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{{Short description|Clinical research to establish the characteristics of COVID-19 vaccines}}
{{cs1 config|name-list-style=vanc|display-authors=6}}{{Pp-semi-indef}}
{{Use dmy dates|date=July 2022}}
{{more medical citations needed|date=January 2023}}
{{Further|COVID-19 vaccine}}
{{COVID-19 pandemic sidebar|expanded=medical}}
'''COVID-19 vaccine clinical research''' uses [[clinical research]] to establish the characteristics of COVID-19 [[COVID-19 vaccine|vaccine]]s. These characteristics include [[#Efficacy|efficacy]], [[#Effectiveness|effectiveness]], and safety. {{As of|2022|November}}, 40 vaccines are authorized by at least one national [[regulation of therapeutic goods|regulatory authority]] for public use:<ref name="london2">{{#invoke:cite web || date=12 July 2021|title=COVID-19 vaccine tracker (Refresh URL to update)|url=https://vac-lshtm.shinyapps.io/ncov_vaccine_landscape/|access-date=10 March 2021|publisher=[[London School of Hygiene & Tropical Medicine]] |website=vac-lshtm.shinyapps.io}}</ref><ref>{{#invoke:cite web || date = 12 July 2021 | title = Approved Vaccines | url = https://covid19.trackvaccines.org/vaccines/approved/ | publisher = COVID 19 Vaccine Tracker, McGill University }}</ref><!-- This lead section is transcluded at [[COVID-19 vaccine#Clinical research]]. Any references used in the lead should be defined. -->
* one [[DNA vaccine]]: [[ZyCoV-D]]<ref>{{cite web | vauthors=Biswas S | title=Zydus Cadila: India approves world's first DNA Covid vaccine | website=BBC News | date=20 August 2021 | url=https://www.bbc.com/news/world-asia-india-57774294 | access-date=5 August 2022 | archive-date=8 August 2022 | archive-url=https://web.archive.org/web/20220808085948/http://www.bbc.com/news/world-asia-india-57774294 | url-status=live }}</ref>
* four [[RNA vaccine]]s: [[Pfizer–BioNTech COVID-19 vaccine|Pfizer–BioNTech]],<ref>{{cite press release | title=FDA Approves First COVID-19 Vaccine | website=U.S. Food and Drug Administration | date=23 August 2021 | url=https://www.fda.gov/news-events/press-announcements/fda-approves-first-covid-19-vaccine | access-date=5 August 2022 | archive-date=23 August 2021 | archive-url=https://web.archive.org/web/20210823143040/https://www.fda.gov/news-events/press-announcements/fda-approves-first-covid-19-vaccine | url-status=live }}</ref> [[Moderna COVID-19 vaccine|Moderna]],<ref>{{cite press release | title=Coronavirus (COVID-19) Update: FDA Authorizes Moderna and Pfizer-BioNTech COVID-19 Vaccines for Children Down to 6 Months of Age | website=U.S. Food and Drug Administration | date=17 June 2022 | url=https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-moderna-and-pfizer-biontech-covid-19-vaccines-children | access-date=5 August 2022 | archive-date=17 June 2022 | archive-url=https://web.archive.org/web/20220617134729/https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-moderna-and-pfizer-biontech-covid-19-vaccines-children | url-status=live }}</ref> [[Walvax COVID-19 vaccine|Walvax]], and [[HGC019|Gemcovac]]
* twelve [[inactivated vaccine]]s: [[Chinese Academy of Medical Sciences COVID-19 vaccine|Chinese Academy of Medical Sciences]],<ref name="Hotez"/><ref name="Yicai Global 20210609">{{cite web | vauthors=Shihua T, Jinyu L, Wei X, Wen W, Difan F, Yushuo Z | title=China's Sixth Covid-19 Vaccine Is Approved for Emergency Use | website=Yicai Global | date=9 June 2021 | url=https://www.yicaiglobal.com/news/china-sixth-covid-19-vaccine-is-approved-for-emergency-use | access-date=5 August 2022 | archive-date=13 April 2022 | archive-url=https://web.archive.org/web/20220413082804/https://www.yicaiglobal.com/news/china-sixth-covid-19-vaccine-is-approved-for-emergency-use | url-status=live }}</ref> [[CoronaVac]],<ref name="Hotez"/> [[Covaxin]],<ref name="Hotez"/> [[CoviVac (Russia COVID-19 vaccine)|CoviVac]], [[COVIran Barekat]], [[FAKHRAVAC]], [[Minhai COVID-19 vaccine|Minhai-Kangtai]], [[QazCovid-in|QazVac]], Sinopharm [[Sinopharm BIBP COVID-19 vaccine|BIBP]],<ref name="Hotez"/> [[Sinopharm WIBP COVID-19 vaccine|WIBP]], [[Turkovac]], and [[Valneva COVID-19 vaccine|VLA2001]].<ref name="Hotez"/>
* six [[viral vector vaccine]]s: [[Sputnik Light]], [[Sputnik V]], [[Oxford–AstraZeneca]], [[Convidecia]], [[Janssen COVID-19 vaccine|Janssen]], and [[BBV154|iNCOVACC]]
* sixteen [[subunit vaccine]]s: [[Abdala (vaccine)|Abdala]], [[Corbevax]],<ref name="Hotez"/> [[COVAX-19]], [[EpiVacCorona]], [[IndoVac]], [[MVC COVID-19 vaccine|MVC-COV1901]],<ref name="Hotez"/> [[Noora (vaccine)|Noora]], [[Novavax COVID-19 vaccine|Novavax]],<ref name="Hotez"/> [[Razi Cov Pars]], [[Sanofi–GSK COVID-19 vaccine|Sanofi–GSK]], [[Sinopharm CNBG COVID-19 vaccine|Sinopharm CNBG]], [[Skycovione]], [[Soberana 02]],<ref name="Hotez"/> [[Soberana Plus]], [[V-01]], and [[ZF2001]].<ref name="Hotez"/>
* one [[virus-like particle]] vaccine: [[CoVLP]]<ref name="Hotez"/>

{{As of|2022|June}}, 353 vaccine candidates are in various stages of development, with 135 in [[clinical research]], including 38 in [[Phases of clinical research#Phase I|phase&nbsp;I trials]], 32 in [[Phases of clinical research#Phase II|phase&nbsp;I–II trials]], 39 in [[Phases of clinical research#Phase III|phase&nbsp;III trials]], and 9 in [[Phases of clinical research#Phase IV|phase&nbsp;IV development]].<ref name="london2" />
{{Toclimit|3}}

==Formulation==
A wide variety of technologies are being used to formulate vaccines against COVID-19. The development and deployment of [[mRNA vaccine]]s and [[viral vector vaccine]]s has been outstandingly rapid and can be described as revolutionary. However, global [[vaccine equity]] against COVID-19 has not been achieved. Conventional vaccine manufacturing approaches using [[whole inactivated virus]] (WIV), protein-based [[subunit vaccine]]s, and [[virus-like particle]]s (VLPs) may offer advantages in the development of vaccines for use in low- and middle-income countries ([[LMIC]]s) and in addressing vaccine access gaps.<ref name="Hotez"/>

Many vaccine candidates use [[Immunologic adjuvant|adjuvants]] to enhance immunogenicity, as part of the delivery system or as an accompanying immune stimulant.<ref>{{cite journal | vauthors = Le TT, Cramer JP, Chen R, Mayhew S | title = Evolution of the COVID-19 vaccine development landscape | journal = Nature Reviews. Drug Discovery | volume = 19 | issue = 10 | pages = 667–668 | date = October 2020 | pmid = 32887942 | doi = 10.1038/d41573-020-00151-8 | s2cid = 221503034 | doi-access = free | title-link = doi }}</ref><ref name="Xu">{{cite journal | vauthors = Wang ZB, Xu J | title = Better Adjuvants for Better Vaccines: Progress in Adjuvant Delivery Systems, Modifications, and Adjuvant-Antigen Codelivery | journal = Vaccines | volume = 8 | issue = 1 | pages = 128 | date = March 2020 | pmid = 32183209 | pmc = 7157724 | doi = 10.3390/vaccines8010128 | doi-access = free | title-link = doi }}</ref> Vaccine adjuvant formulations using [[Aluminium|aluminum salts]] or "alum" may be particularly effective for technologies using inactivated COVID-19 virus and for recombinant protein-based or vector-based vaccines.<ref name="Hotez"/><ref name="wang">{{cite journal | vauthors = Wang J, Peng Y, Xu H, Cui Z, Williams RO | title = The COVID-19 Vaccine Race: Challenges and Opportunities in Vaccine Formulation | journal = AAPS PharmSciTech | volume = 21 | issue = 6 | pages = 225 | date = August 2020 | pmid = 32761294 | pmc = 7405756 | doi = 10.1208/s12249-020-01744-7 }}</ref>

==Status==

=== Clinical trials ===
{{Main|Clinical trial}}
The clinical trial process typically consists of three phases, each following the success of the prior phase. Trials are doubly blind in that neither the researcher nor the subject know whether they receive the vaccine or a placebo. Each phase involves randomly-selected subjects who are randomly assigned to serve either as recipients are controls:
* Phase I trials test primarily for safety and preliminary dosing in healthy subjects. Dozens of subjects.
* Phase II trials evaluate [[immunogenicity]], dose levels (efficacy based on [[biomarker]]s) and adverse effects.<ref name="Vaccines.gov">{{#invoke:cite web || title=Vaccine Safety – Vaccines |url=https://www.vaccines.gov/basics/safety|archive-url=https://web.archive.org/web/20200422073442/https://www.vaccines.gov/basics/safety|archive-date=22 April 2020|url-status=live|access-date=13 April 2020|publisher=US Department of Health and Human Services}}</ref><ref name="fda-ddp">{{#invoke:cite web || date=4 January 2018|title=The drug development process|url=https://www.fda.gov/patients/learn-about-drug-and-device-approvals/drug-development-process|archive-url=https://web.archive.org/web/20200222182002/https://www.fda.gov/patients/learn-about-drug-and-device-approvals/drug-development-process|archive-date=22 February 2020|url-status=live|access-date=12 April 2020|publisher=U.S. [[Food and Drug Administration]] (FDA)}}</ref> Hundreds of subjects. Sometimes Phase&nbsp;I and II trials are combined.<ref name="fda-ddp" />
* Phase III trials typically involve more participants at multiple sites, include a [[control group]], and test effectiveness of the vaccine to prevent the disease (an "interventional" or "pivotal" trial), while monitoring for [[adverse effect]]s at the selected dose.<ref name="Vaccines.gov" /><ref name="fda-ddp" /> Safety, efficacy, and [[clinical endpoint]]s may vary, including the definition of side effects, infection or amount of transmission, and whether the vaccine prevents moderate or severe infection.<ref name="cohen6-19">{{#invoke:cite journal || vauthors = Cohen J | title = Pandemic vaccines are about to face the real test | journal = Science | volume = 368 | issue = 6497 | pages = 1295–1296 | date = June 2020 | pmid = 32554572 | doi = 10.1126/science.368.6497.1295 | bibcode = 2020Sci...368.1295C | doi-access = free | title-link = doi }}</ref><ref name="cdc-eff">{{#invoke:cite web || date=29 January 2016|title=How flu vaccine effectiveness and efficacy are measured|url=https://www.cdc.gov/flu/vaccines-work/effectivenessqa.htm?CDC_AA_refVal=https%3A%2F%2Fwww.cdc.gov%2Fflu%2Fprofessionals%2Fvaccination%2Feffectivenessqa.htm|archive-url=https://web.archive.org/web/20200507083203/https://www.cdc.gov/flu/vaccines-work/effectivenessqa.htm?CDC_AA_refVal=https%3A%2F%2Fwww.cdc.gov%2Fflu%2Fprofessionals%2Fvaccination%2Feffectivenessqa.htm|archive-date=7 May 2020|url-status=live|access-date=6 May 2020|publisher=U.S. [[Centers for Disease Control and Prevention]] (CDC) }}</ref><ref>{{#invoke:cite web || date=18 May 2012|title=Principles of epidemiology, Section 8: Concepts of disease occurrence|url=https://www.cdc.gov/csels/dsepd/ss1978/lesson1/section8.html|archive-url=https://web.archive.org/web/20200406212227/https://www.cdc.gov/csels/dsepd/ss1978/lesson1/section8.html|archive-date=6 April 2020|url-status=live|access-date=6 May 2020|publisher=U.S. [[Centers for Disease Control and Prevention]] (CDC) }}</ref>

A clinical trial design in progress may adopt an [[Adaptive design (medicine)|"adaptive design"]]. If accumulating data provide insights about the treatment, the endpoints or other aspects or the trial can be adjusted.<ref name="pallmann">{{#invoke:cite journal || vauthors = Pallmann P, Bedding AW, Choodari-Oskooei B, Dimairo M, Flight L, Hampson LV, Holmes J, Mander AP, Odondi L, Sydes MR, Villar SS, Wason JM, Weir CJ, Wheeler GM, Yap C, Jaki T | title = Adaptive designs in clinical trials: why use them, and how to run and report them | journal = BMC Medicine | volume = 16 | issue = 1 | pages = 29 | date = February 2018 | pmid = 29490655 | pmc = 5830330 | doi = 10.1186/s12916-018-1017-7 |doi-access=free}}</ref><ref name="fda-adaptive">{{#invoke:cite web || date=1 November 2019|title=Adaptive designs for clinical trials of drugs and biologics: Guidance for industry |url=https://www.fda.gov/media/78495/download|archive-url=https://web.archive.org/web/20191213234438/https://www.fda.gov/media/78495/download|archive-date=13 December 2019|url-status=live|access-date=3 April 2020|publisher=U.S. [[Food and Drug Administration]] (FDA)|format=PDF}}</ref> Adaptive designs may shorten trial durations and use fewer subjects, possibly expediting decisions, avoiding duplication of research efforts, and enhancing coordination of design changes.<ref name="pallmann" /><ref name="solidarity-vacc2">{{#invoke:cite web || date=9 April 2020|title=An international randomised trial of candidate vaccines against COVID-19: Outline of Solidarity vaccine trial |url=https://www.who.int/blueprint/priority-diseases/key-action/Outline_CoreProtocol_vaccine_trial_09042020.pdf|archive-url=https://web.archive.org/web/20200512115627/https://www.who.int/blueprint/priority-diseases/key-action/Outline_CoreProtocol_vaccine_trial_09042020.pdf|archive-date=12 May 2020|url-status=live|access-date=9 May 2020|publisher=[[World Health Organization]] (WHO)}}</ref>

===Vaccine candidates in human trials===
The table below shows various vaccine candidates and the phases which they had completed per the references. Current phases are also shown along with other details.
{| class="wikitable mw-collapsible mw-collapsed"
| '''COVID-19 candidate vaccines in Phase I–III trials'''
|-
| {{COVID-19 vaccine candidates}}
|}
<!--Template is at: [[Template:COVID-19 vaccine candidates]] -->

==== Homologous prime-boost vaccination ====
{{anchor|Homologous prime-boost vaccination}}
In July 2021, the U.S. [[Food and Drug Administration]] (FDA) and the [[Centers for Disease Control and Prevention]] (CDC) issued a joint statement reporting that a booster dose is not necessary for those who have been fully vaccinated.<ref name="FDA PR 20210708">{{cite press release |title=Joint CDC and FDA Statement on Vaccine Boosters |date=8 July 2021 |url=https://www.fda.gov/news-events/press-announcements/joint-cdc-and-fda-statement-vaccine-boosters |access-date=9 July 2021 |website=U.S. [[Food and Drug Administration]] (FDA) |archive-date=9 July 2021 |archive-url=https://web.archive.org/web/20210709192721/http://www.fda.gov/news-events/press-announcements/joint-cdc-and-fda-statement-vaccine-boosters |url-status=live }} {{PD-notice}}</ref>

In August 2021, the FDA and the CDC authorized the use of an additional mRNA vaccine dose for immunocompromised individuals.<ref>{{cite press release |title=Coronavirus (COVID-19) Update: FDA Authorizes Additional Vaccine Dose for Certain Immunocompromised Individuals |date=12 August 2021 |url=https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-additional-vaccine-dose-certain-immunocompromised |access-date=13 August 2021 |website=U.S. [[Food and Drug Administration]] (FDA) |archive-date=7 December 2021 |archive-url=https://web.archive.org/web/20211207181329/https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-additional-vaccine-dose-certain-immunocompromised |url-status=live }}</ref><ref>{{#invoke:cite web || date=13 August 2021 |title=COVID-19 Vaccines for Moderately to Severely Immunocompromised People |url=https://www.cdc.gov/coronavirus/2019-ncov/vaccines/recommendations/immuno.html |access-date=13 August 2021 |website=U.S. [[Centers for Disease Control and Prevention]] (CDC) }}</ref> The authorization was extended to cover other specific groups in September 2021.<ref>{{cite press release | title=FDA Authorizes Booster Dose of Pfizer-BioNTech COVID-19 Vaccine for Certain Populations | website=U.S. [[Food and Drug Administration]] (FDA) | date=22 September 2021 | url=https://www.fda.gov/news-events/press-announcements/fda-authorizes-booster-dose-pfizer-biontech-covid-19-vaccine-certain-populations | access-date=23 September 2021 | archive-date=8 December 2021 | archive-url=https://web.archive.org/web/20211208015251/https://www.fda.gov/news-events/press-announcements/fda-authorizes-booster-dose-pfizer-biontech-covid-19-vaccine-certain-populations | url-status=live }}</ref><ref>{{#invoke:cite web || title=Advisory committee recommends many be offered Covid vaccine boosters | website=[[Stat (website)|Stat News]] | date=23 September 2021 | url=https://www.statnews.com/2021/09/23/covid19-vaccine-boosters-cdc-acip/ | access-date=23 September 2021}}</ref><ref>{{#invoke:cite news || title=C.D.C. Chief C.D.C. Chief Overrules Agency Panel and Endorses Pfizer Boosters for Frontline Workers | website=The New York Times | date=24 September 2021 | url=https://www.nytimes.com/2021/09/24/world/covid-boosters-vaccine-cdc-director.html | access-date=24 September 2021}}</ref>

In October 2021, the FDA and the CDC authorized the use of either homologous or heterologous vaccine booster doses.<ref name="FDA 20211020">{{#invoke:cite web || title=Coronavirus (COVID-19) Update: FDA Takes Additional Actions on the Use of a Booster Dose for COVID-19 Vaccines | website=U.S. Food and Drug Administration | date=21 October 2021 | url=https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-takes-additional-actions-use-booster-dose-covid-19-vaccines | access-date=22 October 2021}} {{PD-notice}}</ref><ref name="CDC 20211021">{{#invoke:cite web || title=CDC Expands Eligibility for COVID-19 Booster Shots | website=[[Centers for Disease Control and Prevention]] (CDC) | date=21 October 2021 | url=https://www.cdc.gov/media/releases/2021/p1021-covid-booster.html | access-date=22 October 2021}} {{PD-notice}}</ref>

{{Anchor|Heterologous prime-boost vaccination}}

==== Heterologous prime-boost vaccination ====

The [[World Health Organization]] (WHO) defines heterologous prime-boost immunization as the "administration of two different vectors or delivery systems expressing the same or overlapping antigenic inserts."<ref>{{#invoke:cite web || title=WHO Technical Consultation: Heterologous Prime-Boost Immunization in Ebola vaccine development and testing, licensure and use; 21 November 2014 |url=https://www.who.int/immunization/research/meetings_workshops/Agenda_ebola_primeboost_nov14.pdf |website=[[World Health Organization]] (WHO) |access-date=10 December 2021 |location=Geneva |date=9 February 2015}}</ref> A heterologous scheme can sometimes be more immunogenic than some homologous schemes.<ref name="Heterologous-PBV-2009">{{#invoke:cite journal || vauthors = Lu S | title = Heterologous prime-boost vaccination | journal = Current Opinion in Immunology | volume = 21 | issue = 3 | pages = 346–351 | date = June 2009 | pmid = 19500964 | pmc = 3743086 | doi = 10.1016/j.coi.2009.05.016 }}</ref>

In October 2021, the FDA and the CDC authorized the use of either homologous or heterologous vaccine booster doses.<ref name="FDA 20211020" /><ref name="CDC 20211021" />

Some experts believe that [[Heterologous vaccine|heterologous]] [[Booster dose|prime-boost]] vaccination courses can boost immunity, and several studies have begun to examine this effect.<ref>{{#invoke:cite journal || vauthors = Ledford H | title = Could mixing COVID vaccines boost immune response? | journal = Nature | volume = 590 | issue = 7846 | pages = 375–376 | date = February 2021 | pmid = 33547431 | doi = 10.1038/d41586-021-00315-5 | bibcode = 2021Natur.590..375L | s2cid = 231946137 }}</ref> Despite the absence of clinical data on the efficacy and safety of such heterologous combinations, Canada and several European countries have recommended a heterologous second dose for people who have received the first dose of the [[Oxford–AstraZeneca|Oxford–AstraZeneca vaccine]].<ref>{{#invoke:cite news || date=22 June 2021 |title=Angela Merkel receives Moderna dose after first AstraZeneca shot |work=Al Jazeera |url=https://www.aljazeera.com/news/2021/6/22/angela-merkel-moderna-after-first-astrazeneca-vaccine |access-date=28 June 2021}}</ref>

In February 2021, the [[Oxford Vaccine Group]] launched the Com-COV vaccine trial to investigate heterologous prime-boost courses of different COVID-19 vaccines.<ref>{{#invoke:cite news || date=30 March 2021 |title=Getting One Vaccine Is Good. How About Mix-and-Match? |work=[[The New York Times]] |url=https://www.nytimes.com/2021/03/30/health/coronavirus-vaccine-astrazeneca-pfizer.html |access-date=30 June 2021}}</ref> As of June 2021, the group is conducting two phase II studies: Com-COV and Com-COV2.<ref>{{#invoke:cite web || title=About |url=https://comcovstudy.org.uk/about |access-date=28 June 2021 |website=Com-COV}}</ref>

In Com-COV, the two heterologous combinations of the [[Oxford–AstraZeneca]] and [[Pfizer–BioNTech COVID-19 vaccine|Pfizer–BioNTech]] vaccines were compared with the two homologous combinations of the same vaccines, with an interval of 28 or 84 days between doses.<ref name="ISRCTN69254139" /><ref>{{cite SSRN |title=Safety and Immunogenicity Report from the Com-COV Study – a Single-Blind Randomised Non-Inferiority Trial Comparing Heterologous And Homologous Prime-Boost Schedules with An Adenoviral Vectored and mRNA COVID-19 Vaccine |date=June 2021 |ssrn=3874014}}</ref>{{unreliable medical source|reason=preprint|date=July 2021}}

In Com-COV2, the first dose is the Oxford–AstraZeneca vaccine or the Pfizer vaccine, and the second dose is the [[Moderna COVID-19 vaccine|Moderna vaccine]], the [[Novavax COVID-19 vaccine|Novavax vaccine]], or a homologous vaccine equal to the first dose, with an interval of 56 or 84 days between doses.<ref name="ISRCTN27841311" />

A study in the UK is evaluating annual heterologous boosters by randomly combining the following vaccines: [[Oxford–AstraZeneca]], [[Pfizer–BioNTech COVID-19 vaccine|Pfizer–BioNTech]], [[Moderna COVID-19 vaccine|Moderna]], [[Novavax COVID-19 vaccine|Novavax]], [[VLA2001]], [[CureVac COVID-19 vaccine|CureVac]], and [[Janssen COVID-19 vaccine|Janssen]].<ref name="ISRCTN73765130">{{#invoke:cite journal || vauthors = Faust S |date=June 2021 |title=Evaluating COVID-19 Vaccination Boosters |url=https://www.isrctn.com/ISRCTN73765130 | journal = ISRCTN Registry |doi=10.1186/ISRCTN73765130 |s2cid=240704676 |id=ISRCTN73765130 |access-date=7 September 2021 |doi-access=free}}</ref>

On 16 December, WHO recommendations on heterologous vaccinations suggested a general trend of increased immunogenicity when one of the doses is of an mRNA vaccine, particularly as the last dose. The immunogenicity of a homologous mRNA course is roughly equivalent to a heterologous scheme involving a vector vaccine and an mRNA vaccine. However, the WHO has emphasized the need to address many evidence gaps in heterologous regimens, including duration of protection, optimal interval between doses, influence of fractional dosing, effectiveness against variants and long-term safety.<ref>{{cite tech report |type=Guidance |title=Interim recommendations for heterologous COVID-19 vaccine schedules |id=WHO/2019-nCoV/vaccines/SAGE_recommendation/heterologous_schedules/2021.1 |institution=[[World Health Organization]] (WHO) |date=16 December 2021 |url=https://www.who.int/publications/i/item/WHO-2019-nCoV-vaccines-SAGE-recommendation-heterologous-schedules |access-date=23 December 2021 |archive-date=24 December 2021 |archive-url=https://web.archive.org/web/20211224000815/https://www.who.int/publications/i/item/WHO-2019-nCoV-vaccines-SAGE-recommendation-heterologous-schedules |url-status=live }}</ref>

{| class="wikitable sortable mw-collapsible"
|+Heterologous second dose regimes in clinical trial
|-
!scope="col"|First dose
!scope="col"|Second dose
!scope="col"|Schedules
!scope="col"|Current phase (participants), periods and locations
|-
|{{br list|Oxford–AstraZeneca|Pfizer–BioNTech}}
|{{br list|Oxford–AstraZeneca|Pfizer–BioNTech}}
|{{br list|Days 0 and 28|Days 0 and 84}}
|{{ClinicalStudyInfo |phase=2 |participants=820
 |references=<ref name="ISRCTN69254139">{{#invoke:cite journal || vauthors = Stuart A, Shaw R, Walker L |date=August 2021 |title=Comparing coronavirus (COVID-19) vaccine schedule combinations |doi=10.1186/ISRCTN69254139 |id=ISRCTN69254139 |website=ISRCTN Registry|s2cid=242713503 |doi-access=free}}</ref>
 |whenwhere=Feb{{ndash}}Aug 2021, United Kingdom}}
|-
|[[Sputnik Light]]
|{{br list|Oxford–AstraZeneca|[[Moderna COVID-19 vaccine|Moderna]]|[[Sinopharm BIBP COVID-19 vaccine|Sinopharm BIBP]]}}
|
|{{ClinicalStudyInfo |phase=2 |participants=121
 |references=<ref>{{cite press release |title=Combination of the first component of Sputnik V vaccine (Sputnik Light vaccine) with vaccines by AstraZeneca, Sinopharm and Moderna demonstrates high safety profile during the study in Argentina's Buenos-Aires province |date=4 August 2021 |publisher=Russian Direct Investment Fund |location=Moscow |url=https://rdif.ru/Eng_fullNews/7035/ |access-date=5 August 2021 |archive-date=5 August 2021 |archive-url=https://web.archive.org/web/20210805212219/https://rdif.ru/Eng_fullNews/7035/ |url-status=dead }}</ref>
 |whenwhere=Feb{{ndash}}Aug 2021, Argentina}}
|-
|{{br list|Oxford–AstraZeneca|Pfizer–BioNTech}}
|{{br list|Oxford–AstraZeneca|Pfizer–BioNTech|Moderna|[[Novavax COVID-19 vaccine|Novavax]]}}
|Days 0 and 56{{ndash}}84
|{{ClinicalStudyInfo |phase=2 |participants=1050
 |references=<ref name="ISRCTN27841311">{{#invoke:cite journal || vauthors = Vichos I, Snape M |date=12 March 2021 |title=Comparing COVID-19 vaccine schedule combinations – stage 2 |url=https://www.isrctn.com/ISRCTN27841311 |doi=10.1186/ISRCTN27841311 |id=ISRCTN27841311 |access-date=9 July 2021 |website=ISRCTN Registry|s2cid=243068742 |doi-access=free}}</ref>
 |whenwhere=Mar 2021{{snd}}Sep 2022, United Kingdom}}
|-
|[[Convidecia]]
|[[ZF2001]]
|{{br list|Days 0 and 28|Days 0 and 56}}
|{{ClinicalStudyInfo |phase=4 |participants=120
 |references=<ref name="NCT04833101">{{#invoke:cite journal || date=6 April 2021 |title=Study on Sequential Immunization of Recombinant COVID-19 Vaccine (Ad5 Vector) and RBD-based Protein Subunit Vaccine |url=https://clinicaltrials.gov/ct2/show/NCT04833101 |id=NCT04833101 |access-date=9 July 2021 |website=ClinicalTrials.gov}}</ref>
 |whenwhere=Apr{{ndash}}Dec 2021, China}}
|-
|Oxford–AstraZeneca
|Pfizer–BioNTech
|Days 0 and 28
|{{ClinicalStudyInfo |phase=2 |participants=676
 |references=<ref name="NCT04860739">{{#invoke:cite journal || date=27 April 2021 |title=Vaccination With COMIRNATY in Subjects With a VAXZEVRIA First Dose (CombiVacS) |url=https://clinicaltrials.gov/ct2/show/NCT04860739 |id=NCT04860739 |access-date=9 July 2021 |website=ClinicalTrials.gov}}</ref>
 |whenwhere=Apr 2021{{snd}}Apr 2022, Spain}}
|-
|{{br list|Oxford–AstraZeneca|Pfizer–BioNTech|Moderna}}
|{{br list|Pfizer–BioNTech|Moderna}}
|{{br list|Days 0 and 28|Days 0 and 112}}
|{{ClinicalStudyInfo |phase=2 |participants=1200
 |references=<ref name="NCT04894435">{{#invoke:cite journal || date=20 May 2021 |title=Mix and Match of the Second COVID-19 Vaccine Dose for Safety and Immunogenicity (MOSAIC) |url=https://clinicaltrials.gov/ct2/show/NCT04894435 |id=NCT04894435 |access-date=9 July 2021 |website=ClinicalTrials.gov}}</ref>
 |whenwhere=May 2021{{snd}}Mar 2023, Canada}}
|-
|{{br list|Pfizer–BioNTech|Moderna}}
|{{br list|Pfizer–BioNTech|Moderna}}
|Days 0 and 42
|{{ClinicalStudyInfo |phase=2 |participants=400
 |references=<ref name="NCT04900467">{{#invoke:cite journal || date=25 May 2021 |title=Compare Immunological Efficacy of a Vaccine Regimen Combining Two Covid19 mRNA Vaccines (Pfizer-BioNTech and Moderna) With That of a Homologous Vaccination of Each Covid19 mRNA Vaccine (ARNCOMBI) |url=https://clinicaltrials.gov/ct2/show/NCT04900467 |id=NCT04900467 |access-date=9 July 2021 |website=ClinicalTrials.gov}}</ref>
 |whenwhere=May 2021{{snd}}Jan 2022, France}}
|-
|Oxford–AstraZeneca
|Pfizer–BioNTech
|{{br list|Days 0 and 28|Days 0 and 21{{ndash}}49}}
|{{ClinicalStudyInfo |phase=2 |participants=3000
 |references=<ref name="NCT04907331">{{#invoke:cite journal || date=28 May 2021 |title=Heterologous Vaccination With an Vaxzevria (ChAdOx1-S) Prime and a Comirnaty (BNT162b2) Boost Compared With Homolog Vaccination With Vaxzervria (Prime/Boost) or Comirnaty (Prime/Boost) (HeVacc) |url=https://clinicaltrials.gov/ct2/show/NCT04907331 |id=NCT04907331 |access-date=9 July 2021 |website=ClinicalTrials.gov}}</ref>
 |whenwhere=May{{ndash}}Dec 2021, Austria}}
|-
|[[Janssen COVID-19 vaccine|Janssen]]
|{{br list|Pfizer–BioNTech|Janssen|Moderna}}
|Days 0 and 84
|{{ClinicalStudyInfo |phase=2 |participants=432
 |references=<ref name="NCT04927936">{{ClinicalTrialsGov|NCT04927936|A Trial Among HealthCare Workers (HCW) Vaccinated With Janssen Vaccine: the SWITCH Trial (SWITCH)}}</ref>
 |whenwhere=Jun 2021{{snd}}Sep 2022, Netherlands}}
|}

{| class="wikitable sortable mw-collapsible"
|+Heterologous booster dose regimes in clinical trial
|-
!scope="col"|Initial course
!scope="col"|Booster dose
!scope="col"|Interval
!scope="col"|Current phase (participants), periods and locations
|-
|[[CoronaVac]] (2 doses)
|{{br list|CoronaVac|[[Pfizer–BioNTech COVID-19 vaccine|Pfizer–BioNTech]]|[[Oxford–AstraZeneca]]}}
|19 weeks or more
|{{ClinicalStudyInfo |phase=4 |participants=2017878
 |references=<ref>{{cite press release |date=7 October 2021 |title=Chile realiza primer estudio a nivel mundial sobre uso de dosis de refuerzo en vacunas inactivadas: Aumenta efectividad en prevención y hospitalización por COVID-19 |trans-title=Chile conducts the first study worldwide on inactivated vaccine boosters: increased effectiveness against disease and hospitalization due to COVID-19 |language=Spanish |url=https://www.minsal.cl/chile-realiza-primer-estudio-a-nivel-mundial-sobre-uso-de-dosis-de-refuerzo-en-vacunas-inactivadas-aumenta-efectividad-en-prevencion-y-hospitalizacion-por-covid-19/ |publisher=Ministry of Health of Chile |access-date=11 November 2021 |archive-date=11 November 2021 |archive-url=https://web.archive.org/web/20211111192236/https://www.minsal.cl/chile-realiza-primer-estudio-a-nivel-mundial-sobre-uso-de-dosis-de-refuerzo-en-vacunas-inactivadas-aumenta-efectividad-en-prevencion-y-hospitalizacion-por-covid-19/ |url-status=live }}</ref><ref>{{#invoke:cite news || title=Elderly Chileans line up for booster jabs to reinforce CoronaVac vaccine |url=https://www.reuters.com/world/americas/elderly-chileans-line-up-booster-jabs-reinforce-coronavac-vaccine-2021-08-11/ |access-date=17 November 2021 |work=Reuters |date=11 August 2021}}</ref>
 |whenwhere=Aug{{ndash}}Nov 2021, Chile}}
|}

==Efficacy==
<section begin=excerpt/>[[File:BNT162b2 vaccine efficacy data.png|thumb|upright=1.2|Cumulative incidence curves for symptomatic COVID-19 infections after the first dose of the Pfizer–BioNTech vaccine (tozinameran) or placebo in a double-blind clinical trial (red: placebo; blue: tozinameran)<ref name=":11">{{#invoke:cite web || date=10 December 2020|title=FDA Briefing Document: Pfizer–BioNTech COVID-19 Vaccine|url=https://www.fda.gov/media/144245/download|access-date=1 January 2021|publisher=U.S. [[Food and Drug Administration]] (FDA)|format=PDF}}</ref>]]

[[Vaccine efficacy]] is the reduction in risk of getting the disease by vaccinated participants in a controlled trial compared with the risk of getting the disease by unvaccinated participants.<ref name="NYT-20201120">{{#invoke:cite news || author-link=Carl Zimmer |date=20 November 2020 |title=2 Companies Say Their Vaccines Are 95% Effective. What Does That Mean? You might assume that 95 out of every 100 people vaccinated will be protected from Covid-19. But that's not how the math works. |work=[[The New York Times]] |url=https://www.nytimes.com/2020/11/20/health/covid-vaccine-95-effective.html |access-date=21 November 2020 |vauthors=Zimmer C}}</ref> An efficacy of 0% means that the vaccine does not work (identical to placebo). An efficacy of 50% means that there are half as many cases of infection as in unvaccinated individuals.{{citation needed|date=July 2021}}

COVID-19 vaccine efficacy may be adversely affected if the arm is held improperly or squeezed so the vaccine is [[subcutaneous injection|injected subcutaneously]] instead of [[intramuscular injection|into the muscle]].<ref>{{#invoke:cite web||url=https://www.nbcmiami.com/news/donotsqueezemyarm-doctor-sounds-alarm-on-how-to-properly-inject-covid-19-vaccine/2353866/|title=#DoNotSqueezeMyArm: Doctor Sounds Alarm on How to Properly Inject COVID-19 Vaccine| vauthors = Odzer A |date=January 2021 }}</ref><ref>{{#invoke:cite journal || vauthors = Ng JY | title = Inadvertent subcutaneous injection of COVID-19 vaccine | journal = Postgraduate Medical Journal | volume = 97 | issue = 1148 | pages = 400 | date = June 2021 | pmid = 33589486 | pmc = 7886662 | doi = 10.1136/postgradmedj-2021-139870 }}</ref> The CDC guidance is to not repeat doses that are administered subcutaneously.<ref>{{#invoke:cite web||url=https://www.cdc.gov/vaccines/covid-19/downloads/covid19-vaccine-errors-deviations.pdf|title=COVID-19 Vaccine Administration Errors and Deviations|publisher=CDC}}</ref>

It is not straightforward to compare the efficacies of the different vaccines because the trials were run with different populations, geographies, and variants of the virus.<ref>{{#invoke:cite web || vauthors = Branswell H | title=Comparing three Covid-19 vaccines: Pfizer, Moderna, J&J | website=[[Stat (website)|Stat]] | date=2 February 2021 | url=https://www.statnews.com/2021/02/02/comparing-the-covid-19-vaccines-developed-by-pfizer-moderna-and-johnson-johnson/ | access-date=28 February 2021}}</ref> In the case of COVID-19 prior to the advent of the delta variant, it was thought that a vaccine [[Intrinsic activity|efficacy]] of 67% may be enough to slow the pandemic, but the current vaccines do not confer [[sterilizing immunity]],<ref>{{#invoke:cite web||date=16 August 2021 |title=Bharat's Intranasal Covid-19 Vaccine Moves Forward |url=https://www.pharmalive.com/bharats-intranasal-covid-19-vaccine-moves-forward/}}</ref> which is necessary to prevent transmission. Vaccine efficacy reflects disease prevention, a poor indicator of transmissibility of SARS‑CoV‑2 since asymptomatic people can be highly infectious.<ref name="RandolphHE2020May">{{#invoke:cite journal || vauthors = Randolph HE, Barreiro LB | title = Herd Immunity: Understanding COVID-19 | journal = Immunity | volume = 52 | issue = 5 | pages = 737–741 | date = May 2020 | pmid = 32433946 | pmc = 7236739 | doi = 10.1016/j.immuni.2020.04.012 }}</ref> The US [[Food and Drug Administration]] (FDA) and the [[European Medicines Agency]] (EMA) set a cutoff of 50% as the efficacy required to approve a COVID-19 vaccine, with the lower limit of the 95% [[confidence interval]] being greater than 30%.<ref>{{#invoke:cite web || title=The FDA's cutoff for Covid-19 vaccine effectiveness is 50 percent. What does that mean?|url=https://www.nbcnews.com/health/health-news/fda-s-cutoff-covid-19-vaccine-effectiveness-50-percent-what-n1245506|access-date=8 January 2021|website=[[NBCNews.com]]| date=3 November 2020}}</ref><ref>{{#invoke:cite web || title=EMA sets 50% efficacy goal – with flexibility – for COVID vaccines|url=https://www.raps.org/news-and-articles/news-articles/2020/11/for-ema-50-efficacy-with-flexibility-is-goal-for-c|access-date=8 January 2021|website=Regulatory Affairs Professionals Society (RAPS)}}</ref><ref>{{#invoke:cite journal || vauthors = Krause P, Fleming TR, Longini I, Henao-Restrepo AM, Peto R | title = COVID-19 vaccine trials should seek worthwhile efficacy | journal = Lancet | volume = 396 | issue = 10253 | pages = 741–743 | date = September 2020 | pmid = 32861315 | pmc = 7832749 | doi = 10.1016/S0140-6736(<span class="ltr">20</span>)31821-3 | title-link = doi | doi-access = free }}</ref> Aiming for a realistic population vaccination coverage rate of 75%, and depending on the actual [[basic reproduction number]], the necessary effectiveness of a COVID-19 vaccine is expected to need to be at least 70% to prevent an epidemic and at least 80% to extinguish it without further measures, such as social distancing.<ref name="efficacy-needed">{{#invoke:cite journal || vauthors = Bartsch SM, O'Shea KJ, Ferguson MC, Bottazzi ME, Wedlock PT, Strych U, McKinnell JA, Siegmund SS, Cox SN, Hotez PJ, Lee BY | title = Vaccine Efficacy Needed for a COVID-19 Coronavirus Vaccine to Prevent or Stop an Epidemic as the Sole Intervention | journal = American Journal of Preventive Medicine | volume = 59 | issue = 4 | pages = 493–503 | date = October 2020 | pmid = 32778354 | pmc = 7361120 | doi = 10.1016/j.amepre.2020.06.011 | doi-access = free | title-link = doi }}</ref><section end=excerpt/>

The observed substantial efficacy of certain mRNA vaccines even after partial (1-dose) immunization<ref>{{#invoke:cite web||date=17 December 2020 |title=FDA Briefing Document for mRNA 1273 |website=[[Food and Drug Administration]] |url=https://www.fda.gov/media/144434/download |url-status=live |access-date=18 August 2021|archive-url=https://web.archive.org/web/20201215124423/https://www.fda.gov/media/144434/download |archive-date=15 December 2020 }}</ref><ref name=":11" /> indicates a non-linear dose-efficacy relation already seen in the phase I-II study.<ref>{{#invoke:cite journal || vauthors = Anderson EJ, Rouphael NG, Widge AT, Jackson LA, Roberts PC, Makhene M, Chappell JD, Denison MR, Stevens LJ, Pruijssers AJ, McDermott AB, Flach B, Lin BC, Doria-Rose NA, O'Dell S, Schmidt SD, Corbett KS, Swanson PA, Padilla M, Neuzil KM, Bennett H, Leav B, Makowski M, Albert J, Cross K, Edara VV, Floyd K, Suthar MS, Martinez DR, Baric R, Buchanan W, Luke CJ, Phadke VK, Rostad CA, Ledgerwood JE, Graham BS, Beigel JH | title = Safety and Immunogenicity of SARS-CoV-2 mRNA-1273 Vaccine in Older Adults | journal = The New England Journal of Medicine | volume = 383 | issue = 25 | pages = 2427–2438 | date = December 2020 | pmid = 32991794 | pmc = 7556339 | doi = 10.1056/NEJMoa2028436 }}</ref>  It suggests that personalization of the vaccine dose (regular dose to the elderly, reduced dose to the healthy young,<ref name="Hunziker 805–820">{{#invoke:cite journal|| vauthors = Hunziker P |date=24 July 2021 |title=Personalized-dose Covid-19 vaccination in a wave of virus Variants of Concern: Trading individual efficacy for societal benefit |url=https://precisionnanomedicine.com/article/26101-personalized-dose-covid-19-vaccination-in-a-wave-of-virus-variants-of-concern-trading-individual-efficacy-for-societal-benefit |journal=Precision Nanomedicine |volume=4 |issue=3 |pages=805–20 |doi=10.33218/001c.26101|doi-access = free | title-link = doi }}</ref> additional booster dose to the immunosuppressed<ref>{{#invoke:cite web|| vauthors = Dooling K |date=13 August 2021 |title=Evidence to Recommendations Framework: Additional doses of mRNA COVID-19 vaccines as part of a primary series for immunocompromised |url =https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2021-08-13/02-COVID-Dooling-508.pdf |website=CDC Advisory Board for Immunization Practices}}</ref>) might allow accelerating vaccination campaigns in settings of limited supplies, thereby shortening the pandemic, as predicted by pandemic modeling.<ref>{{#invoke:cite journal || vauthors = Chen Z, Liu K, Liu X, Lou Y | title = Modelling epidemics with fractional-dose vaccination in response to limited vaccine supply | journal = Journal of Theoretical Biology | volume = 486 | pages = 110085 | date = February 2020 | pmid = 31758966 | doi = 10.1016/j.jtbi.2019.110085 | s2cid = 208254350 | bibcode = 2020JThBi.48610085C | hdl = 10397/94076 }}</ref>

Ranges below are 95% [[confidence interval]]s unless indicated otherwise, and all values are for all participants regardless of age, according to the references for each of the trials. By definition, the [[Margin of error|accuracy]] of the estimates without an associated confidence interval is unknown publicly. Efficacy against severe COVID-19 is the most important, since hospitalizations and deaths are a public health burden whose prevention is a priority.<ref>{{#invoke:cite journal||vauthors=Dean N, Madewell Z |date=5 March 2021 |title=Understanding the spectrum of vaccine efficacy measures |url=https://blogs.bmj.com/bmj/2021/03/05/understanding-the-spectrum-of-vaccine-efficacy-measures/ |journal=The BMJ Opinion |access-date=1 March 2021}}</ref> Authorized and approved vaccines have shown the following efficacies:
<!-- good means the estimate follows WHO, FDA and EMA requirements: minimum 50% point estimate AND minimum 30% lower limit of the 95% CI -->
{| class="wikitable mw-collapsible mw-collapsed"
| '''COVID-19 vaccine efficacy'''
|-
| {{COVID-19 vaccine efficacy}}
|}

===Effectiveness===
{{See also|SARS-CoV-2 Delta variant#Prevention|SARS-CoV-2 Omicron variant#Prevention}}
<noinclude>[[File:2021- COVID-19 death rates by vaccination status - US.svg |thumb |Death rates for unvaccinated Americans substantially exceed those who were vaccinated, with bivalent boosters further reducing the death rate.<ref name=COVIDmortality_2021_2023>{{cite web |title=Data on COVID-19 mortality by vaccination status |url=https://ourworldindata.org/covid-deaths-by-vaccination |publisher=Our World in Data (CDC data) |archive-url=https://web.archive.org/web/20231016112249/https://ourworldindata.org/covid-deaths-by-vaccination |archive-date=16 October 2023 |date=April 2023 |quote=Data source: Centers for Disease Control and Prevention, Vaccine Breakthrough/Surveillance and Analytics Team. |url-status=live }}</ref>]]</noinclude>

Evidence from vaccine use during the pandemic shows vaccination can reduce infection and is most effective at preventing severe COVID-19 symptoms and death, but is less good at preventing mild COVID-19. Efficacy wanes over time but can be maintained with boosters.<ref name="YangJiangLi2023">{{cite journal | vauthors = Yang ZR, Jiang YW, Li FX, Liu D, Lin TF, Zhao ZY, Wei C, Jin QY, Li XM, Jia YX, Zhu FC, Yang ZY, Sha F, Feng ZJ, Tang JL | title = Efficacy of SARS-CoV-2 vaccines and the dose-response relationship with three major antibodies: a systematic review and meta-analysis of randomised controlled trials | journal = The Lancet. Microbe | volume = 4 | issue = 4 | pages = e236–e246 | date = April 2023 | pmid = 36868258 | pmc = 9974155 | doi = 10.1016/S2666-5247(<span class="ltr">22</span>)00390-1 }}</ref> In 2021, the CDC reported that unvaccinated people were 10 times more likely to be hospitalized and 11 times more likely to die than fully vaccinated people.<ref>{{#invoke:cite web|| vauthors = Holcombe M, Waldrop T |date=11 September 2021|title=CDC study: Unvaccinated 11 times more likely to die from Covid-19|url=https://www.cnn.com/2021/09/10/health/us-coronavirus-friday/index.html |access-date=11 September 2021|website=CNN}}</ref><ref>{{#invoke:cite journal || vauthors = Scobie HM, Johnson AG, Suthar AB, Severson R, Alden NB, Balter S, Bertolino D, Blythe D, Brady S, Cadwell B, Cheng I, Davidson S, Delgadillo J, Devinney K, Duchin J, Duwell M, Fisher R, Fleischauer A, Grant A, Griffin J, Haddix M, Hand J, Hanson M, Hawkins E, Herlihy RK, Hicks L, Holtzman C, Hoskins M, Hyun J, Kaur R, Kay M, Kidrowski H, Kim C, Komatsu K, Kugeler K, Lewis M, Lyons BC, Lyons S, Lynfield R, McCaffrey K, McMullen C, Milroy L, Meyer S, Nolen L, Patel MR, Pogosjans S, Reese HE, Saupe A, Sell J, Sokol T, Sosin D, Stanislawski E, Stevens K, Vest H, White K, Wilson E, MacNeil A, Ritchey MD, Silk BJ | title = Monitoring Incidence of COVID-19 Cases, Hospitalizations, and Deaths, by Vaccination Status - 13 U.S. Jurisdictions, April 4-July 17, 2021 | journal = MMWR. Morbidity and Mortality Weekly Report | volume = 70 | issue = 37 | pages = 1284–1290 | date = September 2021 | pmid = 34529637 | pmc = 8445374 | doi = 10.15585/mmwr.mm7037e1 | doi-access = free | url = <!-- Official URL --> https://www.cdc.gov/mmwr/volumes/70/wr/pdfs/mm7037e1-H.pdf }}</ref>

The CDC reported that vaccine effectiveness fell from 91% against [[SARS-CoV-2 Alpha variant|Alpha]] to 66% against Delta.<ref>{{#invoke:cite journal || vauthors = Fowlkes A, Gaglani M, Groover K, Thiese MS, Tyner H, Ellingson K | title = Effectiveness of COVID-19 Vaccines in Preventing SARS-CoV-2 Infection Among Frontline Workers Before and During B.1.617.2 (Delta) Variant Predominance - Eight U.S. Locations, December 2020-August 2021 | language = en-us | journal = MMWR. Morbidity and Mortality Weekly Report | volume = 70 | issue = 34 | pages = 1167–1169 | date = August 2021 | pmid = 34437521 | pmc = 8389394 | doi = 10.15585/mmwr.mm7034e4 | doi-access = free | url = <!-- Official URL --> https://www.cdc.gov/mmwr/volumes/70/wr/pdfs/mm7034e4-H.pdf }}</ref> One expert stated that "those who are infected following vaccination are still not getting sick and not dying like was happening before vaccination."<ref name="TNR">{{cite magazine|vauthors=Schreiber M, Chayka K, Chayka K, Beyerstein L, Beyerstein L, Wilson J, Wilson J, Renault M, Renault M|date=1 July 2021|title=The Delta Covid Variant's Urgent Message for America|magazine=The New Republic|url=https://newrepublic.com/article/162891/delta-covid-variants-urgent-message-america|access-date=28 October 2021|issn=0028-6583|archive-date=28 August 2021|archive-url=https://web.archive.org/web/20210828054506/https://newrepublic.com/article/162891/delta-covid-variants-urgent-message-america|url-status=live}}</ref> By late August 2021, the Delta variant accounted for 99 percent of U.S. cases and was found to double the risk of severe illness and hospitalization for those not yet vaccinated.<ref name=LATimes-delta>{{cite web | title = Among the unvaccinated, Delta variant more than doubles risk of hospitalization | url = https://www.latimes.com/science/story/2021-08-28/hospitalization-risk-doubled-for-unvaccinated-covid-patients-infected-with-delta-variant | archive-url = https://web.archive.org/web/20211108013554/https://www.latimes.com/science/story/2021-08-28/hospitalization-risk-doubled-for-unvaccinated-covid-patients-infected-with-delta-variant | archive-date=8 November 2021 | work = Los Angeles Times | date = 28 August 2021 }}</ref>

In November 2021, a study by the [[ECDC]] estimated that 470,000 lives over the age of 60 had been saved since the start of the vaccination roll-out in the European region.<ref>{{#invoke:cite web||url=https://www.ecdc.europa.eu/en/news-events/who-ecdc-nearly-half-million-lives-saved-covid-19-vaccination|title = WHO/ECDC: Nearly half a million lives saved by COVID-19 vaccination in less than a year|date = 25 November 2021}}</ref>

On 10 December 2021, the [[UK Health Security Agency]] reported that early data indicated a 20- to 40-fold reduction in neutralizing activity for Omicron by sera from Pfizer 2-dose vaccinees relative to earlier strains. After a booster dose (usually with an mRNA vaccine),<ref>{{#invoke:cite web ||title=Coronavirus (COVID-19) booster vaccine |url=https://www.nhs.uk/conditions/coronavirus-covid-19/coronavirus-vaccination/coronavirus-booster-vaccine/ |website=NHS |date=17 September 2021 |publisher=Government Digital Service |access-date=11 December 2021}}</ref> vaccine effectiveness against symptomatic disease was at {{val|70|-|75|u=%}}, and the effectiveness against severe disease was expected to be higher.<ref name="briefing31">{{cite tech report |type=Briefing |title=SARS-CoV-2 variants of concern and variants under investigation in England, technical briefing 31 |id=GOV-10645 |institution=Public Health England |date=10 December 2021 |url=https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1040076/Technical_Briefing_31.pdf |format=PDF |access-date=10 December 2021 |pages=3–5, 20–22 |archive-date=18 December 2021 |archive-url=https://web.archive.org/web/20211218141733/https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1040076/Technical_Briefing_31.pdf |url-status=live }}</ref>

According to early December 2021 CDC data, "unvaccinated adults were about 97 times more likely to die from COVID-19 than fully vaccinated people who had received boosters".<ref name="Gore_2/9/2022">{{#invoke:cite web || vauthors = Gore D | title=Latest CDC Data: Unvaccinated Adults 97 Times More Likely to Die from COVID-19 Than Boosted Adults | website=[[FactCheck.org]] | date=9 February 2022 | url=https://www.factcheck.org/2022/02/scicheck-latest-cdc-data-unvaccinated-adults-97-times-more-likely-to-die-from-covid-19-than-boosted-adults/ | access-date=11 February 2022}}</ref>

A meta-analysis looking into COVID-19 vaccine differences in immunosuppressed individuals found that people with a weakened immune system are less able to produce neutralizing antibodies. For example, organ transplant recipients need three vaccines to achieve [[seroconversion]].<ref>{{cite journal | vauthors = Lee AR, Wong SY, Chai LY, Lee SC, Lee MX, Muthiah MD, Tay SH, Teo CB, Tan BK, Chan YH, Sundar R, Soon YY | title = Efficacy of covid-19 vaccines in immunocompromised patients: systematic review and meta-analysis | journal = BMJ | volume = 376 | pages = e068632 | date = March 2022 | pmid = 35236664 | pmc = 8889026 | doi = 10.1136/bmj-2021-068632 }}</ref> A study on the serologic response to mRNA vaccines among patients with lymphoma, leukemia, and myeloma found that one-quarter of patients did not produce measurable antibodies, varying by cancer type.<ref>{{#invoke:cite journal || vauthors = Greenberger LM, Saltzman LA, Senefeld JW, Johnson PW, DeGennaro LJ, Nichols GL | title = Antibody response to SARS-CoV-2 vaccines in patients with hematologic malignancies | journal = Cancer Cell | volume = 39 | issue = 8 | pages = 1031–1033 | date = August 2021 | pmid = 34331856 | pmc = 8295014 | doi = 10.1016/j.ccell.2021.07.012 }}</ref>

In February 2023, a systematic review in ''[[The Lancet]]'' said that the protection afforded by infection was comparable to that from vaccination, albeit with an increased risk of severe illness and death from the disease of an initial infection.<ref name="SteinNassereldineSorensen2023">{{cite journal | vauthors = Stein C, Nassereldine H, Sorensen RJ, Amlag JO, Bisignano C, Byrne S, Castro E, Coberly K, Collins JK, Dalos J, Daoud F, Deen A, Gakidou E, Giles JR, Hulland EN, Huntley BM, Kinzel KE, Lozano R, Mokdad AH, Pham T, Pigott DM, Reiner Jr RC, Vos T, Hay SI, Murray CJ, Lim SS |title = Past SARS-CoV-2 infection protection against re-infection: a systematic review and meta-analysis | journal = The Lancet | date = February 2023 |volume=401 |issue=10379 |pages=833–842 | issn = 0140-6736 | doi = 10.1016/S0140-6736(<span class="ltr">22</span>)02465-5 | pmid = 36930674|pmc=9998097 | url = }}</ref>

A January 2024 study by the CDC found that staying up to date on the vaccines could reduce the risk of strokes, blood clots and heart attacks related to COVID-19 in people aged 65 years or older or with a condition that makes them more vulnerable to said conditions.<ref>{{cite journal | vauthors = Payne AB |date=2024 |title=Effectiveness of Bivalent mRNA COVID-19 Vaccines in Preventing COVID-19–Related Thromboembolic Events Among Medicare Enrollees Aged ≥65 Years and Those with End Stage Renal Disease — United States, September 2022–March 2023 |url=https://www.cdc.gov/mmwr/volumes/73/wr/mm7301a4.htm |journal=MMWR. Morbidity and Mortality Weekly Report |language=en-us |volume=73 |issue=1 |pages=16–23 |doi=10.15585/mmwr.mm7301a4 |pmid=38206877 |issn=0149-2195 |pmc=10794061 |access-date=14 January 2024 |archive-date=14 January 2024 |archive-url=https://web.archive.org/web/20240114091805/https://www.cdc.gov/mmwr/volumes/73/wr/mm7301a4.htm |url-status=live }}</ref><ref>{{cite web | vauthors = Mole B |date=2024-01-12 |title=COVID shots protect against COVID-related strokes, heart attacks, study finds |url=https://arstechnica.com/science/2024/01/covid-shots-cut-covid-related-stroke-clot-heart-attack-risk-by-50-in-65/ |access-date=2024-01-14 |website=Ars Technica |language=en-us |archive-date=14 January 2024 |archive-url=https://web.archive.org/web/20240114091805/https://arstechnica.com/science/2024/01/covid-shots-cut-covid-related-stroke-clot-heart-attack-risk-by-50-in-65/ |url-status=live }}</ref>

====Studies====
Real-world studies of vaccine [[Phases of clinical research#Efficacy vs effectiveness|effectiveness]] measure the extent to which a certain vaccine prevents infection, symptoms, hospitalization and death for the vaccinated individuals in a large population under routine conditions.<ref>{{#invoke:cite web || title=What is the difference between efficacy and effectiveness? |url=https://www.gavi.org/vaccineswork/what-difference-between-efficacy-and-effectiveness |publisher=[[GAVI|Gavi, the Vaccine Alliance]] (GAVI) |access-date=21 April 2021 |date=18 November 2020}}</ref>
* In Israel, among the 715,425 individuals vaccinated by the mRNA vaccines from 20 December 2020, to 28 January 2021, starting seven days after the second shot, only 317 people (0.04%) displayed mild/moderate COVID-19 symptoms and only 16 people (0.002%) were hospitalized.<ref>{{#invoke:cite web || url=https://edition.cnn.com/world/live-news/coronavirus-pandemic-vaccine-updates-01-29-21/h_a52c58a8bb72bb98f7668ed869afb927|title=Israel's health data suggests Pfizer and Moderna vaccines may be more effective than we thought| vauthors = Tal A, Cohen E |work=CNN|date=29 January 2021|access-date=27 March 2021}}</ref>
* CDC reported that under real-world conditions, mRNA vaccine effectiveness was 90% against infections regardless of symptom status; while effectiveness of partial immunization was 80%.<ref>{{#invoke:cite journal || vauthors = Thompson MG, Burgess JL, Naleway AL, Tyner HL, Yoon SK, Meece J, Olsho LE, Caban-Martinez AJ, Fowlkes A, Lutrick K, Kuntz JL, Dunnigan K, Odean MJ, Hegmann KT, Stefanski E, Edwards LJ, Schaefer-Solle N, Grant L, Ellingson K, Groom HC, Zunie T, Thiese MS, Ivacic L, Wesley MG, Lamberte JM, Sun X, Smith ME, Phillips AL, Groover KD, Yoo YM, Gerald J, Brown RT, Herring MK, Joseph G, Beitel S, Morrill TC, Mak J, Rivers P, Harris KM, Hunt DR, Arvay ML, Kutty P, Fry AM, Gaglani M | title = Interim Estimates of Vaccine Effectiveness of BNT162b2 and mRNA-1273 COVID-19 Vaccines in Preventing SARS-CoV-2 Infection Among Health Care Personnel, First Responders, and Other Essential and Frontline Workers - Eight U.S. Locations, December 2020-March 2021 | journal = MMWR. Morbidity and Mortality Weekly Report | volume = 70 | issue = 13 | pages = 495–500 | date = April 2021 | pmid = 33793460 | pmc = 8022879 | doi = 10.15585/mmwr.mm7013e3 | doi-access = free | url = <!-- Official URL --> https://www.cdc.gov/mmwr/volumes/70/wr/pdfs/mm7013e3-H.pdf }}</ref>
* In the UK, 15,121 health care workers from 104 hospitals who had tested negative for antibodies prior to the study, were followed by [[Reverse transcription polymerase chain reaction|RT-PCR tests]] twice a week from 7&nbsp;December 2020 to 5&nbsp;February 2021, a study compared the positive results for the 90.7% vaccinated share of their cohort with the 9.3% unvaccinated share, and found that the Pfizer-BioNTech vaccine reduced all infections (including asymptomatic), by 72% (58–86%) three weeks after the first dose and 86% (76–97%) one week after the second dose, while Alpha was dominant.<ref>{{cite SSRN |title=Effectiveness of BNT162b2 mRNA Vaccine Against Infection and COVID-19 Vaccine Coverage in Healthcare Workers in England, Multicentre Prospective Cohort Study (the SIREN Study) |date=February 2021 |ssrn=3790399 |vauthors=Hall VJ, Foulkes S, Saei A, Andrews N, Oguti B, Charlett A, Wellington E, Stowe J, Gillson N, Atti A, Islam J, Karagiannis I, Munro K, Khawam J, Chand MA, Brown C, Ramsay ME, Bernal JL, Hopkins S |collaboration=The SIREN Study Group }}</ref>{{Update inline|reason=Information from the outdated preliminary results. Please update based on the definitive results in the reference named 'UKstudy' in the table below.|date=May 2021}}
* In Israel a study conducted from 17 January to 6&nbsp;March 2021, found that Pfizer/BioNTech reduced asymptomatic Alpha infections by 94% and symptomatic COVID-19 infections by 97%.<ref>{{#invoke:cite web || url=https://www.pfizer.com/news/press-release/press-release-detail/real-world-evidence-confirms-high-effectiveness-pfizer|website=Pfizer |title=Real-World Evidence Confirms High Effectiveness of Pfizer–BioNTech COVID-19 Vaccine and Profound Public Health Impact of Vaccination One Year After Pandemic Declared|publisher=|date=11 March 2021|access-date=1 April 2021}}</ref>
* A study on the Queensland Population having only ever been exposed to the Omicron strain of COVID-19 found vaccine effectiveness against symptomatic hospitalizations to be 70% in the general population and similar for First Nations peoples.<ref name="nrs_cq_vax">{{cite journal | vauthors = Smoll NR, Al Imam MH, Shulz C, Booy R, Khandaker G | title = The effectiveness of vaccination for preventing hospitalisation with COVID-19 in regional Queensland: a data linkage study | journal = The Medical Journal of Australia | volume = 219 | issue = 4 | pages = 162–165 | date = August 2023 | pmid = 37400415 | doi = 10.5694/mja2.52019 | s2cid = 259323931 | doi-access = free }}</ref>
* A study among pre-surgical patients across the [[Mayo Clinic]] system in the United States, showed that mRNA vaccines were 80% protective against asymptomatic infections.<ref name="MCSstudy">{{#invoke:cite journal || vauthors = Tande AJ, Pollock BD, Shah ND, Farrugia G, Virk A, Swift M, Breeher L, Binnicker M, Berbari EF | title = Impact of the Coronavirus Disease 2019 (COVID-19) Vaccine on Asymptomatic Infection Among Patients Undergoing Preprocedural COVID-19 Molecular Screening | journal = Clinical Infectious Diseases | volume = 74 | issue = 1 | pages = 59–65 | date = January 2022 | pmid = 33704435 | pmc = 7989519 | doi = 10.1093/cid/ciab229 | doi-access = free | title-link = doi }}</ref>
* A UK study found that a single dose of the [[Oxford–AstraZeneca COVID-19 vaccine]] is about {{Estimate|73|27|90|unit=%|mini=auto}} effective in people aged 70 and older.<ref name="azd1222effectiveness">{{#invoke:cite journal || vauthors = Lopez Bernal J, Andrews N, Gower C, Robertson C, Stowe J, Tessier E, Simmons R, Cottrell S, Roberts R, O'Doherty M, Brown K, Cameron C, Stockton D, McMenamin J, Ramsay M | title = Effectiveness of the Pfizer-BioNTech and Oxford-AstraZeneca vaccines on covid-19 related symptoms, hospital admissions, and mortality in older adults in England: test negative case-control study | journal = BMJ | volume = 373 | pages = n1088 | date = May 2021 | pmid = 33985964 | pmc = 8116636 | doi = 10.1136/bmj.n1088 }}</ref>
* A study finds that nearly all teenagers admitted to intensive care units because of COVID-19 were unvaccinated.<ref>{{#invoke:cite web|| vauthors = Ellis R |title=Almost All Teens in ICU With COVID Were Unvaccinated: Study|url=https://www.webmd.com/vaccines/covid-19-vaccine/news/20220114/unvaccinated-teens-in-icu|access-date=|website=WebMD}}</ref>

====Pregnancy and fertility====
Studies have not observed a correlation between COVID vaccination and fertility.<ref>{{cite news |date=2022-01-20 |title=COVID-19 vaccination does not reduce chances of conception, study suggests |language=EN |publisher=[[National Institutes of Health]] |url=https://www.nih.gov/news-events/news-releases/covid-19-vaccination-does-not-reduce-chances-conception-study-suggests |access-date=10 May 2022 |archive-date=13 May 2022 |archive-url=https://web.archive.org/web/20220513005951/https://www.nih.gov/news-events/news-releases/covid-19-vaccination-does-not-reduce-chances-conception-study-suggests |url-status=live }}</ref><ref>{{cite journal | vauthors = Wesselink A, Hatch E, Rothman K, Wang T, Willis M, Yland J, Crowe H, Geller R, Willis S, Perkins R, Regan A, Levinson J, Mikkelsen E, Wise L | title = A Prospective Cohort Study of COVID-19 Vaccination, SARS-CoV-2 Infection, and Fertility | journal = American Journal of Epidemiology | date = January 20, 2022 | volume = 191 | issue = 8 | pages = 1383–1395 | pmid = 35051292 | pmc = 8807200 | doi = 10.1093/aje/kwac011 }}</ref>

A UK study found COVID vaccination is safe for pregnant women and is associated with a 15% decrease in the odds of stillbirth. Vaccination is recommended for pregnant women because pregnancy increases the risk of severe COVID. Researchers at [[St George's, University of London]], and the [[Royal College of Obstetricians and Gynaecologists]] investigated 23 published studies and trials involving 117,552 vaccinated pregnant women. There was no increased risk of complications during pregnancy. Almost all pregnant women admitted to UK hospitals with COVID were unvaccinated.<ref>{{cite news | vauthors = Sample I |date=2022-05-10 |title=Covid vaccines safe for pregnant women and cut stillbirth risk, says review |language=en-GB |work=The Guardian |url=https://www.theguardian.com/world/2022/may/10/covid-vaccines-safe-for-pregnant-women-and-cut-stillbirth-risk-says-review |issn=0261-3077 |access-date=10 May 2022 |archive-date=10 May 2022 |archive-url=https://web.archive.org/web/20220510104357/https://www.theguardian.com/world/2022/may/10/covid-vaccines-safe-for-pregnant-women-and-cut-stillbirth-risk-says-review |url-status=live }}</ref><ref>{{cite journal | vauthors = Prasad S, Kalafat E, Blakeway H, Townsend R, O'Brien P, Morris E, Draycott T, Thangaratinam S, Le Doare K, Ladhani S, von Dadelszen P, Magee LA, Heath P, Khalil A | title = Systematic review and meta-analysis of the effectiveness and perinatal outcomes of COVID-19 vaccination in pregnancy | journal = Nature Communications | volume = 13 | issue = 1 | pages = 2414 | date = May 2022 | pmid = 35538060 | pmc = 9090726 | doi = 10.1038/s41467-022-30052-w | s2cid = 248695866 | bibcode = 2022NatCo..13.2414P }}</ref>

A US study of 46,079 pregnancies concluded that COVID vaccination is safe and does not raise the risk of preterm birth or small size babies.<ref>{{cite journal | vauthors = Lipkind HS, Vazquez-Benitez G, DeSilva M, Vesco KK, Ackerman-Banks C, Zhu J, Boyce TG, Daley MF, Fuller CC, Getahun D, Irving SA, Jackson LA, Williams JT, Zerbo O, McNeil MM, Olson CK, Weintraub E, Kharbanda EO | title = Receipt of COVID-19 Vaccine During Pregnancy and Preterm or Small-for-Gestational-Age at Birth - Eight Integrated Health Care Organizations, United States, December 15, 2020-July 22, 2021 | journal = MMWR. Morbidity and Mortality Weekly Report | volume = 71 | issue = 1 | pages = 26–30 | date = January 2022 | pmid = 34990445 | pmc = 8735559 | doi = 10.15585/mmwr.mm7101e1 | doi-access = free | url = <!-- Official URL --> https://www.cdc.gov/mmwr/volumes/71/wr/pdfs/mm7101e1-H.pdf | access-date = 31 July 2022 | archive-url = https://web.archive.org/web/20220407175526/https://www.cdc.gov/mmwr/volumes/71/wr/pdfs/mm7101e1-h.pdf | url-status = live | archive-date = 7 April 2022 }}</ref>

{{COVID-19 vaccine effectiveness}}

===Variants===
<noinclude>{{See also|Variants of SARS-CoV-2}}</noinclude>
{{Update|section|inaccurate=yes|date=July 2021|reason=Information taken from WHO's COVID-19 Weekly Epidemiological Update is outdated and inaccurate. The latest version now is 20 July, edition 49}}
[[File:WHO EN 3 Working Together 03Mar2021.webm|thumb|279x279px|[[World Health Organization]] video describing how variants proliferate in unvaccinated areas]]
<!-- Please note this section is transcluded onto the Variants of SARS-CoV-2 page using Template:Excerpt -->

The interplay between the SARS-CoV-2 virus and its human hosts was initially natural but is now being altered by the prompt availability of vaccines.<ref>{{#invoke:cite journal || vauthors = Burioni R, Topol EJ | title = Has SARS-CoV-2 reached peak fitness? | journal = Nature Medicine | volume = 27 | issue = 8 | pages = 1323–1324 | date = August 2021 | pmid = 34155413 | doi = 10.1038/s41591-021-01421-7 | doi-access = free | title-link = doi }}</ref> The potential emergence of a SARS-CoV-2 variant that is moderately or fully resistant to the antibody response elicited by the COVID-19 vaccines may necessitate modification of the vaccines.<ref name=":02">{{#invoke:cite web || author = Office of the Commissioner |date=23 February 2021|title=Coronavirus (COVID-19) Update: FDA Issues Policies to Guide Medical Product Developers Addressing Virus Variants|url=https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-issues-policies-guide-medical-product-developers-addressing-virus|access-date=7 March 2021|website=U.S. [[Food and Drug Administration]] (FDA)}}</ref> The emergence of vaccine-resistant variants is more likely in a highly vaccinated population with uncontrolled transmission.<ref>{{#invoke:cite journal || vauthors = Rella SA, Kulikova YA, Dermitzakis ET, Kondrashov FA | title = Rates of SARS-CoV-2 transmission and vaccination impact the fate of vaccine-resistant strains | journal = Scientific Reports | volume = 11 | issue = 1 | pages = 15729 | date = July 2021 | pmid = 34330988 | pmc = 8324827 | doi = 10.1038/s41598-021-95025-3 }}</ref> Trials indicate many vaccines developed for the initial strain have lower efficacy for some variants against symptomatic COVID-19.<ref name=":8">{{#invoke:cite journal || vauthors = Mahase E | title = Covid-19: Where are we on vaccines and variants? | journal = BMJ | volume = 372 | pages = n597 | date = March 2021 | pmid = 33653708 | doi = 10.1136/bmj.n597 | s2cid = 232093175 | doi-access = free | title-link = doi }}</ref> {{As of|2021|2}}, the US [[Food and Drug Administration]] believed that all FDA authorized vaccines remained effective in protecting against circulating strains of SARS-CoV-2.<ref name=":02" />

====Alpha (lineage B.1.1.7)====
{{Further|SARS-CoV-2 Alpha variant}}

Limited evidence from various preliminary studies reviewed by the WHO indicated retained efficacy/effectiveness against disease from Alpha with the Oxford–AstraZeneca vaccine, Pfizer–BioNTech and Novavax, with no data for other vaccines yet. Relevant to how vaccines can end the pandemic by preventing asymptomatic infection, they have also indicated retained antibody neutralization against Alpha with most of the widely distributed vaccines (Sputnik V, Pfizer–BioNTech, Moderna, CoronaVac, Sinopharm BIBP, Covaxin), minimal to moderate reduction with the Oxford–AstraZeneca and no data for other vaccines yet.<ref name="who-update-variant-impact" />

<noinclude>In December 2020, a new [[Variants of SARS-CoV-2|SARS‑CoV‑2 variant]], the [[SARS-CoV-2 Alpha variant|Alpha variant]] or lineage B.1.1.7, was identified in the UK.<ref>{{cite news |date=18 January 2021 |title=Inside the B.1.1.7 Coronavirus Variant |work=[[The New York Times]] |url=https://www.nytimes.com/interactive/2021/health/coronavirus-mutations-B117-variant.html |access-date=29 January 2021 |archive-date=20 January 2021 |archive-url=https://web.archive.org/web/20210120143819/https://www.nytimes.com/interactive/2021/health/coronavirus-mutations-B117-variant.html |url-status=live }}</ref></noinclude>

Early results suggest protection to the variant from the Pfizer-BioNTech and Moderna vaccines.<ref name="science.sciencemag.org">{{#invoke:cite journal || vauthors = Muik A, Wallisch AK, Sänger B, Swanson KA, Mühl J, Chen W, Cai H, Maurus D, Sarkar R, Türeci Ö, Dormitzer PR, Şahin U | title = Neutralization of SARS-CoV-2 lineage B.1.1.7 pseudovirus by BNT162b2 vaccine-elicited human sera | journal = Science | volume = 371 | issue = 6534 | pages = 1152–1153 | date = March 2021 | pmid = 33514629 | pmc = 7971771 | doi = 10.1126/science.abg6105 | doi-access = free | title-link = doi | bibcode = 2021Sci...371.1152M }}</ref><ref name="nature.b117.B1351">{{#invoke:cite journal || vauthors = Wang P, Nair MS, Liu L, Iketani S, Luo Y, Guo Y, Wang M, Yu J, Zhang B, Kwong PD, Graham BS, Mascola JR, Chang JY, Yin MT, Sobieszczyk M, Kyratsous CA, Shapiro L, Sheng Z, Huang Y, Ho DD | title = Antibody resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7 | journal = Nature | volume = 593 | issue = 7857 | pages = 130–135 | date = May 2021 | pmid = 33684923 | doi = 10.1038/s41586-021-03398-2 | doi-access = free | title-link = doi | bibcode = 2021Natur.593..130W }}</ref>

One study indicated that the [[Oxford–AstraZeneca COVID-19 vaccine]] had an efficacy of 42–89% against Alpha, versus 71–91% against other variants.<ref>{{cite SSRN |title=Efficacy of ChAdOx1 nCoV-19 (AZD1222) Vaccine Against SARS-CoV-2 VOC 202012/01 (B.1.1.7) |date=February 2021 |ssrn=3779160 |vauthors=Emary KR, Golubchik T, Aley PK, Ariani CV, Angus BJ, Bibi S, Blane B, Bonsall D, Cicconi P, Charlton S, Clutterbuck E}}</ref>{{unreliable medical source|reason=preprint|date=July 2021}}

Preliminary data from a clinical trial indicates that the [[Novavax COVID-19 vaccine|Novavax vaccine]] is ~96% effective for symptoms against the original variant and ~86% against Alpha.<ref>{{#invoke:cite journal || vauthors = Mahase E | title = Covid-19: Novavax vaccine efficacy is 86% against UK variant and 60% against South African variant | journal = BMJ | volume = 372 | pages = n296 | date = February 2021 | pmid = 33526412 | doi = 10.1136/bmj.n296 | s2cid = 231730012 | doi-access = free | title-link = doi }}</ref>

====Beta (lineage B.1.351)====
{{Further|SARS-CoV-2 Beta variant}}
Limited evidence from various preliminary studies reviewed by the WHO have indicated reduced efficacy/effectiveness against disease from Beta with the Oxford–AstraZeneca vaccine (possibly substantial), Novavax (moderate), Pfizer–BioNTech and Janssen (minimal), with no data for other vaccines yet. Relevant to how vaccines can end the pandemic by preventing asymptomatic infection, they have also indicated possibly reduced antibody neutralization against Beta with most of the widely distributed vaccines (Oxford–AstraZeneca, Sputnik V, Janssen, Pfizer–BioNTech, Moderna, Novavax; minimal to substantial reduction) except CoronaVac and Sinopharm BIBP (minimal to modest reduction), with no data for other vaccines yet.<ref name="who-update-variant-impact">{{cite tech report |type=Situation report |title=Weekly epidemiological update on COVID-19 – 8 June 2021 |institution=[[World Health Organization]] (WHO) |date=8 June 2021 |url=https://www.who.int/publications/m/item/weekly-epidemiological-update-on-covid-19---8-june-2021 |at=Table 3 |access-date=14 June 2021 |archive-date=15 June 2021 |archive-url=https://web.archive.org/web/20210615112029/https://www.who.int/publications/m/item/weekly-epidemiological-update-on-covid-19---8-june-2021 |url-status=live }}</ref>

Moderna has launched a trial of a vaccine to tackle the [[SARS-CoV-2 Beta variant|Beta variant]] or lineage B.1.351.<ref>{{#invoke:cite web || title=Moderna develops new vaccine to tackle mutant Covid strain | work=[[Financial Times]]|url=https://www.ft.com/content/c0c8f72c-e58e-4319-80c4-0db153ad85db|access-date=30 January 2021 | vauthors = Kuchler H | date=25 January 2021 | url-access=subscription }}</ref> On 17 February 2021, Pfizer announced neutralization activity was reduced by two-thirds for this variant, while stating that no claims about the efficacy of the vaccine in preventing illness for this variant could yet be made.<ref>{{#invoke:cite journal || vauthors = | title = Neutralizing Activity of BNT162b2-Elicited Serum – Preliminary Report | journal = The New England Journal of Medicine | date = February 2021 | pmid = 33596352 | doi = 10.1056/nejmc2102017 | doi-access = free | title-link = doi }}</ref> Decreased neutralizing activity of sera from patients vaccinated with the Moderna and Pfizer-BioNTech vaccines against Beta was later confirmed by several studies.<ref name="nature.b117.B1351" /><ref name="cell.B1351.P1">{{#invoke:cite journal || vauthors = Hoffmann M, Arora P, Groß R, Seidel A, Hörnich BF, Hahn AS, Krüger N, Graichen L, Hofmann-Winkler H, Kempf A, Winkler MS, Schulz S, Jäck HM, Jahrsdörfer B, Schrezenmeier H, Müller M, Kleger A, Münch J, Pöhlmann S | title = SARS-CoV-2 variants B.1.351 and P.1 escape from neutralizing antibodies | journal = Cell | volume = 184 | issue = 9 | pages = 2384–2393.e12 | date = April 2021 | pmid = 33794143 | pmc = 7980144 | doi = 10.1016/j.cell.2021.03.036 | doi-access = free | title-link = doi }}</ref> On 1&nbsp;April 2021, an update on a Pfizer/BioNTech South African vaccine trial stated that the vaccine was 100% effective so far (i.e., vaccinated participants saw no cases), with six of nine infections in the placebo control group being the Beta variant.<ref>{{cite press release |title=Pfizer and BioNTech Confirm High Efficacy and No Serious Safety Concerns Through Up to Six Months Following Second Dose in Updated Topline Analysis of Landmark COVID-19 Vaccine Study |date=1 April 2021 |url=https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-confirm-high-efficacy-and-no-serious |access-date=2 April 2021 |website=Pfizer |archive-date=17 April 2021 |archive-url=https://web.archive.org/web/20210417082319/https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-confirm-high-efficacy-and-no-serious |url-status=live }}</ref>

In January 2021, Johnson & Johnson, which held trials for its [[Janssen COVID-19 vaccine|Janssen vaccine]] in South Africa, reported the level of protection against moderate to severe COVID-19 infection was 72% in the United States and 57% in South Africa.<ref name="NIH_Janssen_2021_Jan">{{cite news |title=Janssen Investigational COVID-19 Vaccine: Interim Analysis of Phase 3 Clinical Data Released |url=https://www.nih.gov/news-events/news-releases/janssen-investigational-covid-19-vaccine-interim-analysis-phase-3-clinical-data-released |access-date=26 March 2023 |work=National Institutes of Health (NIH) |date=29 January 2021 |language=EN |archive-date=26 March 2023 |archive-url=https://web.archive.org/web/20230326200024/https://www.nih.gov/news-events/news-releases/janssen-investigational-covid-19-vaccine-interim-analysis-phase-3-clinical-data-released |url-status=live }}</ref><ref name="BekkerGarrettGoga2022">{{cite journal | vauthors = Bekker LG, Garrett N, Goga A, Fairall L, Reddy T, Yende-Zuma N, Kassanjee R, Collie S, Sanne I, Boulle A, Seocharan I, Engelbrecht I, Davies MA, Champion J, Chen T, Bennett S, Mametja S, Semenya M, Moultrie H, de Oliveira T, Lessells RJ, Cohen C, Jassat W, Groome M, Von Gottberg A, Le Roux E, Khuto K, Barouch D, Mahomed H, Wolmarans M, Rousseau P, Bradshaw D, Mulder M, Opie J, Louw V, Jacobson B, Rowji P, Peter JG, Takalani A, Odhiambo J, Mayat F, Takuva S, Corey L, Gray GE, Brumskine W, Naicker N, Makhaza D, Naicker V, Naidoo L, Spooner E, van Nieuwenhuizen E, Mngadi K, Nchabeleng M, Innes JC, Gill K, Petrick FG, Barnabas S, Badal-Faesen S, Kassim S, Mahoney SH, Lazarus E, Nana A, Maboa RM, Kotze P, Lombaard J, Malan DR, Kotze S, Mohlala P, Ward A, Meintjes G, Urbach D, Patel F, Diacon A, Ahmed K, Grobbelaar C, Mda P, Dubula T, Luabeya A, Mamba MB, Burgess L, Dawson R | title = Effectiveness of the Ad26.COV2.S vaccine in health-care workers in South Africa (the Sisonke study): results from a single-arm, open-label, phase 3B, implementation study | journal = The Lancet | date = March 2022 | volume = 399 | issue = 10330 | pages = 1141–1153 | issn = 0140-6736 | doi = 10.1016/S0140-6736(<span class="ltr">22</span>)00007-1 | pmid = 35305740 | pmc = 8930006 | url = }}</ref><ref name="PreiserFish2022">{{cite journal | vauthors = Preiser W, Fish T | title = Sisonke: reaching several goals together | journal = Lancet | volume = 399 | issue = 10330 | pages = 1095–1097 | date = March 2022 | pmid = 35305727 | pmc = 8930005 | doi = 10.1016/S0140-6736(<span class="ltr">22</span>)00482-2 }}</ref>

On 6 February 2021, the ''[[Financial Times]]'' reported that provisional trial data from a study undertaken by South Africa's [[University of the Witwatersrand]] in conjunction with [[University of Oxford|Oxford University]] demonstrated reduced efficacy of the [[Oxford–AstraZeneca COVID-19 vaccine]] against the variant.<ref>{{cite news |date=6 February 2021 |title=Oxford/AstraZeneca COVID shot less effective against South African variant: study |work=[[Reuters]] |url=https://www.reuters.com/article/us-health-coronavirus-astrazeneca-varian/oxford-astrazeneca-covid-shot-less-effective-against-south-african-variant-study-idUSKBN2A60SH |access-date=8 February 2021 |vauthors=Francis D, Andy B |archive-date=8 February 2021 |archive-url=https://web.archive.org/web/20210208023740/https://www.reuters.com/article/us-health-coronavirus-astrazeneca-varian/oxford-astrazeneca-covid-shot-less-effective-against-south-african-variant-study-idUSKBN2A60SH |url-status=live }}</ref> The study found that in a sample size of 2,000 the AZD1222 vaccine afforded only "minimal protection" in all but the most severe cases of COVID-19.<ref name="BBC55975052">{{cite news |date=8 February 2021 |title=Covid: South Africa halts AstraZeneca vaccine rollout over new variant |work=[[BBC News Online]] |url=https://www.bbc.com/news/world-africa-55975052 |access-date=8 February 2021 |archive-date=8 February 2021 |archive-url=https://web.archive.org/web/20210208002315/https://www.bbc.com/news/world-africa-55975052 |url-status=live }}</ref> On 7&nbsp;February 2021, the [[Minister of Health (South Africa)|Minister for Health]] for South Africa suspended the planned deployment of about a million doses of the vaccine whilst they examine the data and await advice on how to proceed.<ref name=BBC55975052 /><ref>{{cite news |date=7 February 2021 |title=South Africa suspends Oxford-AstraZeneca vaccine rollout after researchers report 'minimal' protection against coronavirus variant |newspaper=[[The Washington Post]] |location=London |url=https://www.washingtonpost.com/world/europe/astrazeneca-oxford-vaccine-south-african-variant/2021/02/07/e82127f8-6948-11eb-a66e-e27046e9e898_story.html |access-date=8 February 2021 |quote=South Africa will suspend use of the coronavirus vaccine being developed by Oxford University and AstraZeneca after researchers found it provided 'minimal protection' against mild to moderate coronavirus infections caused by the new variant first detected in that country. |vauthors=Booth W, Johnson CY |archive-date=8 February 2021 |archive-url=https://web.archive.org/web/20210208005004/https://www.washingtonpost.com/world/europe/astrazeneca-oxford-vaccine-south-african-variant/2021/02/07/e82127f8-6948-11eb-a66e-e27046e9e898_story.html |url-status=live }}</ref>

In a study reported in March<ref>{{ClinicalTrialsGov|NCT04533399|A Phase 2A/B, Randomized, Observer-blinded, Placebo-controlled Study to Evaluate the Efficacy, Immunogenicity, and Safety of a SARS-CoV-2 Recombinant Spike Protein Nanoparticle Vaccine (SARS-CoV-2 rS) With Matrix-M1 Adjuvant in South African Adult Subjects Living Without HIV; and Safety and Immunogenicity in Adults Living With HIV}}</ref> and May 2021,<ref name="Shinde">{{cite journal | vauthors = Shinde V, Bhikha S, Hoosain Z, Archary M, Bhorat Q, Fairlie L, Lalloo U, Masilela MS, Moodley D, Hanley S, Fouche L, Louw C, Tameris M, Singh N, Goga A, Dheda K, Grobbelaar C, Kruger G, Carrim-Ganey N, Baillie V, de Oliveira T, Lombard Koen A, Lombaard JJ, Mngqibisa R, Bhorat AE, Benadé G, Lalloo N, Pitsi A, Vollgraaff PL, Luabeya A, Esmail A, Petrick FG, Oommen-Jose A, Foulkes S, Ahmed K, Thombrayil A, Fries L, Cloney-Clark S, Zhu M, Bennett C, Albert G, Faust E, Plested JS, Robertson A, Neal S, Cho I, Glenn GM, Dubovsky F, Madhi SA | title = Efficacy of NVX-CoV2373 Covid-19 Vaccine against the B.1.351 Variant | journal = The New England Journal of Medicine | volume = 384 | issue = 20 | pages = 1899–1909 | date = May 2021 | pmid = 33951374 | doi = 10.1056/NEJMoa2103055 | pmc = 8091623 | s2cid = 233868860 }}</ref> the efficacy of the [[Novavax COVID-19 vaccine|Novavax vaccine]] (NVX-CoV2373) was tested in a preliminary randomized, placebo-controlled study involving 2684 participants who were negative for COVID at baseline testing. Beta was the predominant variant to occur, with post-hoc analysis indicating a vaccine efficacy of Novavax against Beta of 51.0% for HIV-negative participants.<ref name="Hotez">{{cite journal | vauthors = Hotez PJ, Bottazzi ME | title = Whole Inactivated Virus and Protein-Based COVID-19 Vaccines | journal = Annual Review of Medicine | volume = 73 | issue = 1 | pages = 55–64 | date = January 2022 | pmid = 34637324 | doi = 10.1146/annurev-med-042420-113212 | doi-access = free | title-link = doi | s2cid = 238747462 }}</ref><ref name="Shinde"/>

====Gamma (lineage P.1)====
{{Further|SARS-CoV-2 Gamma variant}}
Limited evidence from various preliminary studies{{when|date=July 2022}} reviewed by the WHO have indicated likely retained efficacy/effectiveness against disease from Gamma with CoronaVac and Sinopharm BIBP, with no data for other vaccines yet. Relevant to how vaccines can end the pandemic by preventing asymptomatic infection, they have also indicated retained antibody neutralization against Gamma with Oxford–AstraZeneca and CoronaVac (no to minimal reduction) and slightly reduced neutralization with Pfizer–BioNTech and Moderna (minimal to moderate reduction), with no data for other vaccines yet.<ref name="who-update-variant-impact" />

The [[SARS-CoV-2 Gamma variant|Gamma variant]] or lineage P.1 variant (also known as 20J/501Y.V3), initially identified in Brazil, seems to partially escape vaccination with the Pfizer-BioNTech vaccine.<ref name="cell.B1351.P1" />

====Delta (lineage B.1.617.2)====
{{Further|SARS-CoV-2 Delta variant}}
Limited evidence from various preliminary studies{{when|date=July 2022}} reviewed by the WHO have indicated likely retained efficacy/effectiveness against disease from Delta with the Oxford–AstraZeneca vaccine and Pfizer–BioNTech, with no data for other vaccines yet. Relevant to how vaccines can end the pandemic by preventing asymptomatic infection, they have also indicated reduced antibody neutralization against Delta with ''single-dose'' Oxford–AstraZeneca (substantial reduction), Pfizer–BioNTech and Covaxin (modest to moderate reduction), with no data for other vaccines yet.<ref name="who-update-variant-impact" />

<noinclude>In October 2020, a new variant was discovered in India, which was named [[lineage B.1.617]]. There were very few detections until January 2021, but by April it had spread to at least 20 countries in all continents except Antarctica and South America.<ref>{{#invoke:cite web||title=PANGO lineages|url=https://cov-lineages.org/lineages/lineage_B.1.617.html|access-date=18 April 2021|website=cov-lineages.org}}</ref><ref name="Koshy">{{cite news |date=8 April 2021 |title=Coronavirus {{!}} Indian 'double mutant' strain named B.1.617 |work=The Hindu |url=https://www.thehindu.com/news/national/indian-double-mutant-strain-named-b1617/article34274663.ece/amp/ |vauthors=Koshy J |access-date=29 August 2021 |archive-date=26 May 2021 |archive-url=https://web.archive.org/web/20210526012246/https://www.thehindu.com/news/national/indian-double-mutant-strain-named-b1617/article34274663.ece/amp/ |url-status=live }}</ref><ref>{{cite news |date=10 April 2021 |title=India's variant-fuelled second wave coincided with spike in infected flights landing in Canada |newspaper=[[Toronto Sun]] |url=https://torontosun.com/news/local-news/indias-variant-fuelled-second-wave-coincided-with-spike-in-infected-flights-landing-in-canada |access-date=10 April 2021 |archive-date=2 June 2021 |archive-url=https://web.archive.org/web/20210602102218/https://torontosun.com/news/local-news/indias-variant-fuelled-second-wave-coincided-with-spike-in-infected-flights-landing-in-canada |url-status=live }}</ref></noinclude> Mutations present in the [[coronavirus spike protein|spike protein]] in the B.1.617 lineage are associated with reduced antibody neutralization in laboratory experiments.<ref name="edara_2021">{{#invoke:cite journal || vauthors = Edara VV, Pinsky BA, Suthar MS, Lai L, Davis-Gardner ME, Floyd K, Flowers MW, Wrammert J, Hussaini L, Ciric CR, Bechnak S, Stephens K, Graham BS, Bayat Mokhtari E, Mudvari P, Boritz E, Creanga A, Pegu A, Derrien-Colemyn A, Henry AR, Gagne M, Douek DC, Sahoo MK, Sibai M, Solis D, Webby RJ, Jeevan T, Fabrizio TP | title = Infection and Vaccine-Induced Neutralizing-Antibody Responses to the SARS-CoV-2 B.1.617 Variants | journal = The New England Journal of Medicine | volume = 385 | issue = 7 | pages = 664–666 | date = August 2021 | pmid = 34233096 | pmc = 8279090 | doi = 10.1056/NEJMc2107799 }}</ref><ref name="planas_2021">{{#invoke:cite journal || vauthors = Planas D, Veyer D, Baidaliuk A, Staropoli I, Guivel-Benhassine F, Rajah MM, Planchais C, Porrot F, Robillard N, Puech J, Prot M, Gallais F, Gantner P, Velay A, Le Guen J, Kassis-Chikhani N, Edriss D, Belec L, Seve A, Courtellemont L, Péré H, Hocqueloux L, Fafi-Kremer S, Prazuck T, Mouquet H, Bruel T, Simon-Lorière E, Rey FA, Schwartz O | title = Reduced sensitivity of SARS-CoV-2 variant Delta to antibody neutralization | journal = Nature | volume = 596 | issue = 7871 | pages = 276–280 | date = August 2021 | pmid = 34237773 | doi = 10.1038/s41586-021-03777-9 | s2cid = 235775860 | doi-access = free | title-link = doi | bibcode = 2021Natur.596..276P }}</ref><noinclude> The variant has frequently been referred to as a 'Double mutant', even though in this respect it is not unusual.<ref name="617BBC">{{cite news |vauthors=Biswas S |date=25 March 2021 |title='Double mutant': What are the risks of India's new Covid-19 variant |work=[[BBC News Online]] |url=https://www.bbc.co.uk/news/world-asia-india-56517495 |access-date=11 April 2021 |archive-date=28 April 2021 |archive-url=https://web.archive.org/web/20210428080913/https://www.bbc.co.uk/news/world-asia-india-56517495 |url-status=live }}</ref> the latter two of which may cause it to easily avoid antibodies.<ref>{{cite news |vauthors=Haseltine WA |date=12 April 2021 |title=An Indian SARS-CoV-2 Variant Lands In California. More Danger Ahead? |work=Forbes |url=https://www.forbes.com/sites/williamhaseltine/2021/04/12/an-indian-sars-cov-2-variant-lands-in-california-more-danger-ahead/ |access-date=14 April 2021 |archive-date=13 April 2021 |archive-url=https://web.archive.org/web/20210413213549/https://www.forbes.com/sites/williamhaseltine/2021/04/12/an-indian-sars-cov-2-variant-lands-in-california-more-danger-ahead/ |url-status=live }}</ref> In an update on 15 April 2021, PHE designated lineage B.1.617 as a 'Variant under investigation', VUI-21APR-01.<ref name="IndiaPHE">{{cite news |date=15 April 2021 |title=Confirmed cases of COVID-19 variants identified in UK |work=Public Health England |url=https://www.gov.uk/government/news/confirmed-cases-of-covid-19-variants-identified-in-uk |access-date=16 April 2021 |archive-date=7 May 2021 |archive-url=https://web.archive.org/web/20210507162335/https://www.gov.uk/government/news/confirmed-cases-of-covid-19-variants-identified-in-uk |url-status=live }}</ref> On 6 May 2021, [[Public Health England]] escalated lineage B.1.617.2 from a Variant Under Investigation to a [[Variant of Concern]] based on an assessment of transmissibility being at least equivalent to the [[SARS-CoV-2 Alpha variant|Alpha variant]].<ref>{{#invoke:cite web ||title=expert reaction to VUI-21APR-02/B.1.617.2 being classified by PHE as a variant of concern |url=https://www.sciencemediacentre.org/expert-reaction-to-vui-21apr-02-b-1-617-2-being-classified-by-phe-as-a-variant-of-concern/?cli_action=1621097773.028 |website= Science Media Centre |date=7 May 2021 |access-date=15 May 2021}}</ref></noinclude>

====Omicron (lineage BA.2 and BA.2.12.2)====
COVID-19 vaccine effectiveness was studied in adults without immunocompromising conditions in 10 US states between December 18, 2021 – June 10, 2022, when Omicron was prevalent. 3 doses of mRNA COVID-19 vaccines was 69% against COVID-19–associated hospitalization 7–119 days after the third vaccine dose and 52% against COVID-19–associated hospitalization more than 4 months after the 3rd dose. Among adults aged ≥50 years, COVID-19 vaccine effectiveness against COVID-19–associated hospitalization ≥120 days after receipt of dose 3 was only 32%, increasing to 66% ≥7 days after the fourth dose.<ref name="cdc">{{cite journal | vauthors = Link-Gelles R, Levy ME, Gaglani M, Irving SA, Stockwell M, Dascomb K, DeSilva MB, Reese SE, Liao IC, Ong TC, Grannis SJ, McEvoy C, Patel P, Klein NP, Hartmann E, Stenehjem E, Natarajan K, Naleway AL, Murthy K, Rao S, Dixon BE, Kharbanda AB, Akinseye A, Dickerson M, Lewis N, Grisel N, Han J, Barron MA, Fadel WF, Dunne MM, Goddard K, Arndorfer J, Konatham D, Valvi NR, Currey JC, Fireman B, Raiyani C, Zerbo O, Sloan-Aagard C, Ball SW, Thompson MG, Tenforde MW | title = Effectiveness of 2, 3, and 4 COVID-19 mRNA Vaccine Doses Among Immunocompetent Adults During Periods when SARS-CoV-2 Omicron BA.1 and BA.2/BA.2.12.1 Sublineages Predominated - VISION Network, 10 States, December 2021-June 2022 | journal = MMWR. Morbidity and Mortality Weekly Report | volume = 71 | issue = 29 | pages = 931–939 | date = July 2022 | pmid = 35862287 | doi = 10.15585/mmwr.mm7129e1 | pmc = 9310634 | url = <!-- Official URL --> https://www.cdc.gov/mmwr/volumes/71/wr/pdfs/mm7129e1-H.pdf | access-date = 31 July 2022 | url-status = live | archive-url = https://web.archive.org/web/20220728171454/http://www.cdc.gov/mmwr/volumes/71/wr/pdfs/mm7129e1-H.pdf | archive-date = 28 July 2022 | doi-access = free }}</ref>

===Effect of neutralizing antibodies===
One study found that the [[in vitro]] concentration ([[titer]]) of [[Neutralizing antibody|neutralizing antibodies]] elicited by a COVID-19 vaccine is a strong [[Correlates of immunity/correlates of protection|correlate of immune protection]]. The relationship between protection and neutralizing activity is [[Nonlinear system|nonlinear]]. A neutralization as low as {{Estimate|3|1|13|unit=%|mini=no}} of the level of [[convalescence]] results in 50% efficacy against severe disease, with {{Estimate|20|14|28|unit=%|mini=yes}} resulting in 50% efficacy against detectable infection. Protection against infection quickly decays, leaving individuals susceptible to mild infections, while protection against severe disease is largely retained and much more durable. The observed half-life of neutralizing titers was 65 days for mRNA vaccines ([[Pfizer–BioNTech COVID-19 vaccine|Pfizer–BioNTech]], [[Moderna COVID-19 vaccine|Moderna]]) during the first 4 months, increasing to 108 days over 8 months. Greater initial efficacy against infection likely results in a higher level of protection against serious disease in the long term (beyond 10 years, as seen in other vaccines such as smallpox, measles, mumps, and rubella), although the authors acknowledge that their simulations consider only protection from neutralizing antibodies and ignore other immune protection mechanisms, such as [[cell-mediated immunity]], which may be more durable. This observation also applies to efficacy against variants and is particularly significant for vaccines with a lower initial efficacy; for example, a 5-fold reduction in neutralization would indicate a reduction in initial efficacy from 95% to 77% against a specific variant, and from a lower efficacy of 70% to 32% against that variant. For the [[Oxford–AstraZeneca COVID-19 vaccine|Oxford–AstraZeneca vaccine]], the observed efficacy is below the predicted 95% confidence interval. It is higher for [[Sputnik V COVID-19 vaccine|Sputnik V]] and the convalescent response, and is within the predicted interval for the other vaccines evaluated ([[Pfizer–BioNTech COVID-19 vaccine|Pfizer–BioNTech]], [[Moderna COVID-19 vaccine|Moderna]], [[Janssen COVID-19 vaccine|Janssen]], [[CoronaVac]], [[Covaxin]], [[Novavax COVID-19 vaccine|Novavax]]).<ref>{{#invoke:cite journal || vauthors = Khoury DS, Cromer D, Reynaldi A, Schlub TE, Wheatley AK, Juno JA, Subbarao K, Kent SJ, Triccas JA, Davenport MP | title = Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection | journal = Nature Medicine | volume = 27 | issue = 7 | pages = 1205–1211 | date = July 2021 | pmid = 34002089 | doi = 10.1038/s41591-021-01377-8 | s2cid = 234769053 }}</ref>

==Side effects==
All vaccines, including COVID-19 ones, can have [[Reactogenicity|minor side effects]] related to the mild trauma associated with the introduction of a foreign substance into the body.<ref name="Hervé">{{cite journal | vauthors = Hervé C, Laupèze B, Del Giudice G, Didierlaurent AM, Tavares Da Silva F | title = The how's and what's of vaccine reactogenicity | journal = npj Vaccines | volume = 4 | issue = 1 | pages = 39 | date = 24 September 2019 | pmid = 31583123 | pmc = 6760227 | doi = 10.1038/s41541-019-0132-6 }}</ref><ref name="Polania">{{cite book | vauthors = Polania Gutierrez JJ, Munakomi S | date = January 2020 | chapter = Intramuscular Injection | chapter-url = https://www.ncbi.nlm.nih.gov/books/NBK556121/ | title = StatPearls | pmid = 32310581 | location = Treasure Island (<span class="ltr">FL</span>) | publisher = StatPearls Publishing | access-date = 30 August 2021 | archive-date = 8 December 2020 | archive-url = https://web.archive.org/web/20201208182850/https://www.ncbi.nlm.nih.gov/books/NBK556121/ | url-status = live }}</ref> These include soreness, redness, rash, and inflammation at the injection site. Other common side effects include fatigue, headache, [[myalgia]] (muscle pain), and [[arthralgia]] (joint pain) which generally resolve within a few days.<ref name="who-back">{{cite report |url=https://apps.who.int/iris/rest/bitstreams/1330343/retrieve |title=Background document on the mRNA-1273 vaccine (Moderna) against COVID-19 |date=February 2021 |publisher=[[World Health Organization]] (WHO) |id=WHO/2019-nCoV/vaccines/SAGE_recommendation/mRNA-1273/background/2021.1 |hdl-access=free |hdl=10665/339218 |access-date=30 August 2021 |archive-date=13 June 2021 |archive-url=https://web.archive.org/web/20210613133906/https://apps.who.int/iris/rest/bitstreams/1330343/retrieve |url-status=live }}</ref>

Serious adverse events that follow the administration of vaccines are of high interest to the public.<ref>{{#invoke:cite journal || vauthors = Montgomery J, Ryan M, Engler R, Hoffman D, McClenathan B, Collins L, Loran D, Hrncir D, Herring K, Platzer M, Adams N, Sanou A, Cooper LT | title = Myocarditis Following Immunization With mRNA COVID-19 Vaccines in Members of the US Military | journal = JAMA Cardiology | volume = 6 | issue = 10 | pages = 1202–1206 | date = October 2021 | pmid = 34185045 | pmc = 8243257 | doi = 10.1001/jamacardio.2021.2833 | doi-access = free | title-link = doi }}</ref> It is important to recognize that the occurrence of an adverse event following vaccination does not necessarily mean that the vaccine caused the adverse event; the health problem may have been unrelated. Reporting of all adverse events, careful followup and statistical analysis of occurrences are required to determine whether or not a specific health problem is more likely to occur after a vaccine is administered.<ref name="Adverse">{{#invoke:cite web ||title=COVID-19 Vaccination |url=https://www.cdc.gov/coronavirus/2019-ncov/vaccines/safety/adverse-events.html |website=Centers for Disease Control and Prevention |access-date=19 April 2022 |date=11 February 2020}}</ref><ref>{{#invoke:cite web ||title=Vaccine Adverse Events Reporting System (VAERS) Help |url=https://wonder.cdc.gov/wonder/help/vaers.html |website=wonder.cdc.gov |access-date=19 April 2022}}</ref><ref name="Hogan"/>

More serious side effects are very rare. Before COVID-19 vaccines such as Moderna and Pfizer/BioNTech were authorized for use in the general population, they had to pass phase III studies involving tens of thousands of people. Any serious side effects that did not appear during that testing are likely to occur less often than ~1 in 10,000 cases. It is important that Phase III trials be diverse, to ensure that safety results apply broadly. It is possible that side effects may affect a population that was not adequately represented during the initial testing. Pregnant women, immunocompromised people, and children are usually excluded from initial studies because they may be at higher risk. Further studies may be done to ensure their safety before vaccines are authorized for use in such populations. Subsequent examinations of the use of COVID vaccines in pregnant people and in children have shown similar outcomes to the general population and do not suggest greater risk for these groups.<ref name="Hogan">{{cite journal | vauthors = Hogan MJ, Pardi N | title = mRNA Vaccines in the COVID-19 Pandemic and Beyond | journal = Annual Review of Medicine | volume = 73 | issue = 1 | pages = 17–39 | date = January 2022 | pmid = 34669432 | doi = 10.1146/annurev-med-042420-112725 | s2cid = 239050929 | doi-access = free }}</ref>

==References==
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