COVID-19 vaccine effectiveness on variants of concern
(Randomized evidence)

Methods

Variants of concern

Description of primary studies

Trial Type Comparisons Design Participants Sample size Overall risk
of bias
Highest assessment
Full description
Intervention 1 Intervention 2
Alpha
Beta
Delta
NCT05033847
National Vaccine and Serum Institute, China; Sinopharm + China National Biotec Group Co + Beijing Institute of Biological Products
Al Kaabi N, Sig Transduct Target, 2022
Updated

Full text
Commentary
Heterologous booster

BBIBP-CorV/BoostNVSI 1-3m

BBIBP-CorV/Boost 1-3m

RCT
Phase 2
Healthy adults with no history of SARS-CoV-2 infection who had previously received a primary series (two doses) of BBIBP-CorV at a single center in United Arab Emirates N=1800
Some concerns
Details

Full description

Gamma
Delta
NCT04672395
Clover Biopharmaceuticals Inc./Dynavax
Bravo L, Lancet, 2022

Full text
Commentary
Commentary
Protein subunit

SCB-2019

Placebo

RCT
Phase 2-3
Healthy adults or with stable chronic conditions, both SARS-CoV-2 seropositive and seronegative, at 31 centers in Belgium, Brazil, Colombia, Philippines, and South Africa. N=30174
Some concerns
Details

Full description

Beta
Gamma
Delta
ChiCTR2100051998
Sinovac Research and Development Co. Ltd.; Anhui Zhifei Longcom Biopharmaceutical + Institute of Microbiology, Chinese Academy of Sciences
Cao Y, Cell Res, 2021

Full text
Commentary
Inactivated virus

CoronaVac/Boost ZF2001

CoronaVac/Boost CoronaVac

RCT
Phase 2
Healthcare professionals with no previous confirmed COVID-19 at a single center in China who had received two doses of CoronaVac in a 28-day interval 4–8 months earlier N=164
Some concerns
Details

Full description

Gamma
ISRCTN89951424
AstraZeneca+University of Oxford
Clemens S, Nat. Commun., 2021

Full text
Commentary
Commentary
Non replicating viral vector

ChAdOx1

MenACWY

RCT
Phase 3
Adults that were SARS-CoV-2 seronegative and with no history of COVID-19 in six centers in Brazil. N=10416 Variant gamma:

Some concerns
Details

Full description

Delta
RBR–9nn3scw
AstraZeneca+University of Oxford/Sinovac/Janssen Pharmaceutical Companies/Pfizer/BioNTech+Fosun Pharma
Costa Clemens SA, Lancet, 2022

Full text
Commentary
Commentary
Non replicating viral vector

CoronaVac/Boost BNT162b2

CoronaVac/Boost ChAd

CoronaVac/Boost AD26

CoronaVac/Boost CoronaVac

RCT
Phase 4
Healthy adults with no history of confirmed covid-19 who had previously received 2 doses of CoronaVac at two centers in Brazil N=1240
Some concerns
Details

Full description

Alpha
NCT04611802
Novavax
Dunkle L M, N Engl J Med, 2021

Full text
Commentary
Protein subunit

NVX-CoV2373

Placebo

RCT
Phase 3
Healthy adults in 113 sites in the USA and 6 in Mexico N=29949
Some concerns
Details

Full description

Alpha
Delta
NCT04641481
Bharat Biotech
Ella R, Lancet, 2021

Full text
Commentary
Inactivated virus

BBV152

Adjuvant

RCT
Phase 3
Adults with no history of SARS-CoV-2 infection who were healthy or had stable chronic medical conditions at 25 centers in India N=25798 Variant delta:

Some concerns
Details Variant alpha:

Some concerns
Details

Full description

Alpha
NCT04400838
AstraZeneca+University of Oxford
Emary K, Lancet, 2021

Full text
Commentary
Non replicating viral vector

ChAdOx1

MenACWY

RCT
Phase 2-3
Adults seronegative at baseline enrolled at 19 study sites in UK N=10673 Variant alpha:

Some concerns
Details

Full description

Alpha
Beta
Gamma
Delta
NCT04636697
Medicago Inc
Hager K, N Engl J Med, 2022
Updated

Full text
Full text
Commentary
Virus-Like particle

CoVLP

Placebo

RCT
Phase 3
Adults including elderly with and without comorbidities, with no previous history of virologically confirmed COVID-19, both seronegative and seropositive, at 85 centers in Argentina, Brazil, Canada, Mexico, the UK, and the USA. N=24141
Some concerns
Details

Full description

Alpha
NCT04526990
CanSino Biological Inc./Beijing Institute of Biotechnology
Halperin SA, Lancet, 2021

Full text
Commentary
Commentary
Non replicating viral vector

Ad5-nCoV

Adjuvant

RCT
Phase 3
Healthy adults with no history of laboratory-confirmed COVID-19 at 66 sites in Argentina, Chile, Mexico, Pakistan, and Russia N=36982
Some concerns
Details

Full description

Alpha
Beta
Gamma
Delta
NCT04614948
Janssen Pharmaceutical Companies
Hardt K, medRxiv, 2022
ENSEMBLE2

Full text
Commentary
Commentary
Non replicating viral vector

Ad26.COV2.S Ad26.COV2.S

Placebo

RCT
Phase 3
Adults, healthy or with stable and well-controlled comorbidities, at 125 centers in Belgium, Brazil, Colombia, France, Germany, The Philippines, South Africa, Spain, UK, and USA N=31835
Some concerns
Details

Full description

Alpha
NCT04614948
Janssen Pharmaceutical Companies
Hardt K, medRxiv, 2022
ENSEMBLE2

Full text
Commentary
Commentary
Non replicating viral vector

Ad26.COV2.S

Placebo

RCT
Phase 3
Adults, healthy or with stable and well-controlled comorbidities, at 125 centers in Belgium, Brazil, Colombia, France, Germany, The Philippines, South Africa, Spain, UK, and USA N=31835
Some concerns
Details

Full description

Alpha
NCT04583995; EudraCT 2020-004123-16
Novavax
Heath P, N Engl J Med, 2021

Full text
Commentary
Protein subunit

NVX-CoV2373

Placebo

RCT
Phase 3
Adults 18 to 84 years old who were healthy or had stable chronic medical conditions with no history of COVID-19 at 33 centres in the UK. N=15187 Variant alpha:

Some concerns
Details

Full description

Delta
TCTR20211004001
Sinovac/Pfizer-BioNTech+Fosun Pharma
Intapiboon P, Vaccines, 2021

Full text
Commentary
Heterologous booster

CoronaVac/boostBNT16(1:2)

CoronaVac/boostBNT(1:5)ID

CoronaVac/boostBNT16

RCT
*
Healthy adults who had reecived 2 doses CoronaVac with no current or known history of SARS-CoV-2 infection at a single center in Thailand N=91
Some concerns
Details

Full description

Alpha
Beta
Delta
NCT04900467; EudraCT: 2021-002174-52
Moderna;Pfizer/BioNTech
Janssen C, EClinicalMedicine, 2022

Full text
Full text
Commentary
Heterologous vaccination scheme

BNT/mRNA-1273

m1273/BNT162b2

BNT162b2

mRNA-1273

RCT
Phase 2
Adults with no known or suspected history of SARS-CoV-2 infection at 17 centers in France. N=414
Some concerns
Details

Full description

Alpha
Delta
NCT04530357
Research Institute for Biological Safety Problems, Rep of Kazakhstan
Khairullin B, SSRN, 2022

Full text
Commentary
Commentary
Inactivated virus

QazCovid-in

Adjuvant

RCT
Phase 3
Healthy adults or those with chronic diseases, with no known or suspected history of COVID-19 at 3 centers in Kazakhstan N=3000
Some concerns
Details

Full description

Alpha
Gamma
NCT04652102; EudraCT 2020-003998-22
CureVac AG
Kremsner P, Lancet Infect Dis, 2022
HERALD

Full text
Commentary
RNA based vaccine

CVnCoV

Placebo

RCT
Phase 2-3
Adults with no history of COVID-19 in 47 centers in Belgium, Germany, The Netherlands, Spain, Argentina, Colombia, Dominican Republic, Mexico, Panama and Peru N=39680
Some concerns
Details

Full description

Beta
NCT04444674
AstraZeneca + University of Oxford
Madhi S, N Engl J Med, 2021
COV005

Full text
Commentary
Non replicating viral vector

ChAdOx1

Placebo

RCT
Phase 1-2
Healthy adult volunteers that were HIV-negative and SARS-CoV-2 infection-free in 7 centres in South Africa N=2026 Variant beta:

Some concerns
Details

Full description

Alpha
Beta
Delta
NCT04368988
Novavax
Mallory R, medRxiv, 2021

Full text
Commentary
Commentary
Protein subunit

NVX-CoV2373 boost

NVX-CoV2373

NVX-CoV2373

Placebo

RCT
Phase 2
Healthy adults (stable comorbidities and confirmed COVID-19 with mild symptoms permitted) who had received 2 doses NVX-CoV2373 or placebo in a trial at 17 centers in Australia and USA N=383 N/A

Full description

Beta
Gamma
Delta
NCT04611243
Sinovac/Pfizer/BioNTech+Fosun Pharma
Mok C K P, Am. J. Respir. Crit., 2022

Full text
Commentary
Inactivated virus

CoronaVac/Boost

CoronaVac/Boost BNT162b2

RCT
*
Adults that had received two doses of CoronaVac but had low immune response against SARS-CoV-2 at two centres in Hong Kong, China N=80
Some concerns
Details

Full description

Beta
Delta
ISRCTN73765130
AstraZeneca + University of Oxford; Janssen Pharmaceutical; Novovax; Moderna + NIAID; Pfizer BioNTech + Fosun Pharma; CureVac AG; Valneva, NIHR, UK
Munro A, Lancet, 2021
COV-BOOST

Full text
Commentary
Heterologous booster

ChadOx1/boostm1273

ChadOx1/boostCVn

ChadOx1/boostBNT(half)

ChadOx1/Placebo

RCT
Phase 2
Adults aged ≥30 years in good physical health at 18 centers in the UK. N=462
Some concerns
Details

Full description

Beta
Delta
ISRCTN73765130
AstraZeneca + University of Oxford; Janssen Pharmaceutical; Novovax; Moderna + NIAID; Pfizer BioNTech + Fosun Pharma; CureVac AG; Valneva, NIHR, UK
Munro A, Lancet, 2021
COV-BOOST

Full text
Commentary
Heterologous booster

BNT162b2/boostm1273

BNT162b2/boostCVn

BNT162b2/boostBNT(half)

BNT162b2/Placebo

RCT
Phase 2
Adults aged ≥30 years in good physical health at 18 centers in the UK. N=439
Some concerns
Details

Full description

Beta
Delta
ISRCTN73765130
AstraZeneca + University of Oxford; Janssen Pharmaceutical; Novovax; Moderna + NIAID; Pfizer BioNTech + Fosun Pharma; CureVac AG; Valneva, NIHR, UK
Munro A, Lancet, 2021
COV-BOOST

Full text
Commentary
Heterologous booster

BNT162b2/boostChAd

BNT162b2/boostNVX

BNT162b2/boostNVX(half)

BNT162b2/Placebo

RCT
Phase 2
Adults aged ≥30 years in good physical health at 18 centers in the UK. N=453
Some concerns
Details

Full description

Beta
Delta
ISRCTN73765130
AstraZeneca + University of Oxford; Janssen Pharmaceutical; Novovax; Moderna + NIAID; Pfizer BioNTech + Fosun Pharma; CureVac AG; Valneva, NIHR, UK
Munro A, Lancet, 2021
COV-BOOST

Full text
Commentary
RNA based vaccine

BNT162b2/boost

BNT162b2/boostVLA

BNT162b2/boostVLA(half)

BNT162b2/boostAd26

BNT162b2/Placebo

RCT
Phase 2
Adults aged ≥30 years in good physical health at 18 centers in the UK. N=545
Some concerns
Details

Full description

Beta
Delta
ISRCTN73765130
AstraZeneca + University of Oxford; Janssen Pharmaceutical; Novovax; Moderna + NIAID; Pfizer BioNTech + Fosun Pharma; CureVac AG; Valneva, NIHR, UK
Munro A , Lancet, 2021
COV-BOOST

Full text
Commentary
Non replicating viral vector

ChadOx1/boost

ChadOx1/boostNVX

ChadOx1/boostNVX(half)

ChadOx1/Placebo

RCT
Phase 2
Adults aged ≥30 years in good physical health at 18 centers in the UK. N=443
Some concerns
Details

Full description

Beta
Delta
ISRCTN73765130
AstraZeneca + University of Oxford; Janssen Pharmaceutical; Novovax; Moderna + NIAID; Pfizer BioNTech + Fosun Pharma; CureVac AG; Valneva, NIHR, UK
Munro A, Lancet, 2021
COV-BOOST

Full text
Commentary
Heterologous booster

ChadOx1/boostBNT

ChadOx1/boostVLA

ChadOx1/boostVLA(half)

ChadOx1/boostAd26

ChadOx1/Placebo

RCT
Phase 2
Adults aged ≥30 years in good physical health at 18 centers in the UK. N=541
Some concerns
Details

Full description

Delta
TCTR20210722003
AstraZeneca+University of Oxford
Nanthapisal S, Vaccine, 2022

Full text
Commentary
Commentary
Non replicating viral vector

CoronaVac/Boost ChAd

CoronaVac/Boost ChAd(LD)

RCT
Phase 2
Healthy adult volunteers with no history or current infection with SARS-CoV-2 who had completed two doses of CoronaVac at 2 centres in Thailand. N=422
Some concerns
Details

Full description

Alpha
Delta
NCT04922788
Nanogen Pharmaceutical Biotechnology JSC.
Nguyen TP, medRxiv, 2022

Full text
Commentary
Commentary
Protein subunit

Nanocovax

Placebo

RCT
Phase 3
Healthy adult without previous or current SARS-CoV-2 infection in four centres in Vietnam. N=13007
Some concerns
Details

Full description

Beta
Gamma
NCT04764422
The Government Pharmaceutical Organization (GPO); PATH; Dynavax
Pitisuttithum P, medRxiv, 2021

Full text
Commentary
Commentary
Inactivated virus

NDV-HXP-S 1mcg

NDV-HXP-S 1mcg + CpG1018

NDV-HXP-S 3mcg

NDV-HXP-S 3mcg + CpG1018

NDV-HXP-S 10mcg

NDV-HXP-S 1mcg

Placebo

RCT
Phase 1
Healthy adults without immunosuppression negative for SARS-CoV-2 antibodies at a single center in Thailand N=210
Some concerns
Details

Full description

Alpha
Beta
Gamma
Delta
NCT05142319
Pfizer/BioNTech+Fosun Pharma; ModernaTX
Poh XY, Clin. Infect. Dis., 2022
PRIBIVAC

Full text
Commentary
RNA based vaccine

BNT162b2/boostm1273

BNT162b2/boostBNT

RCT
3
Adults at a single center in Singapore with no previous history of COVID-19 who had received a primary series of BTN162b2 at least 6 months previously N=100
Some concerns
Details

Full description

Alpha
Beta
Gamma
NCT04505722
Janssen Pharmaceutical Companies
Sadoff J, N Engl J Med, 2022
ENSEMBLE

Full text
Commentary
Non replicating viral vector

Ad26.COV2.S

Placebo

RCT
Phase 3
Adults >18 years of age at 213 centers in Argentina, Brazil, Chile, Colombia, Mexico, Peru, South Africa and USA N=44325 Variant beta:

Some concerns
Details

Full description

Beta
NCT04533399; PACTR202009726132275
Novavax
Shinde V, N Engl J Med, 2021

Full text
Commentary
Protein subunit

NVX-CoV2373

Placebo

RCT
Phase 2
HIV-negative adults (18 to 84 years) and medically stable HIV-positive adults (18 to 64 years) at 16 sites in South Africa N=4406 Variant beta:

Some concerns
Details

Full description

Delta
jRCT2031210470
Shionogi;Pfizer/BioNTech+Fosun Pharma
Shinkai M, medRxiv, 2022

Full text
Commentary
Commentary
Protein subunit

BNT162b2/boostS-268019-b

BNT162b2/boostBNT

RCT
Phase 2-3
Adults who had received 2 doses of BNT162b2 vaccine at least 6 months earlier with no history of SARS-CoV-2 infection at a single centre in Japan N=204
Some concerns
Details

Full description

Beta
Delta
NCT04762680
Sanofi Pasteur+GlaxoSmithKline
Sridhar S, Lancet Infect Dis , 2022

Full text
Commentary
Protein subunit

CoV2 preS dTM 15 mcg

CoV2 preS dTM 10 mcg

CoV2 preS dTM 5 mcg

RCT
Phase 2
Adults with and without prior SARS-CoV-2 infection and risk factors for severe disease at 20 centers in the USA and Honduras N=722
Some concerns
Details

Full description

Beta
Delta
ISRCTN27841311; EudraCT 2021-001275-16
AstraZeneca + University of Oxford / Novavax / Moderna + NIAID
Stuart A, Lancet, 2021
Com-COV2

Full text
Commentary
Commentary
Protein subunit

ChAd/NVX-CoV2373

ChAd/mRNA-1273

ChAdOx1

RCT
Phase 2
Healthy adults over 50 years previously vaccinated with one dose of ChAdOx1 nCoV-19 in 9 centres in the UK N=540
Some concerns
Details

Full description

Beta
Delta
ISRCTN27841311; EudraCT 2021-001275-16
Pfizer BioNTech + Fosun Pharma / Novavax / Moderna + NIAID
Stuart A, Lancet, 2021
Com-COV2

Full text
Commentary
Commentary
Protein subunit

BNT/NVX-CoV2373

BNT/mRNA-1273

BNT162b2

RCT
Phase 2
Adults over 50 years previously vaccinated with one dose of BNT162b2 at 9 centres in the UK N=532
Some concerns
Details

Full description

Beta
NCT04368728
Pfizer/BioNTech+Fosun Pharma
Thomas S, N Engl J Med, 2021

Full text
Commentary
Commentary
RNA based vaccine

BNT162b2

Placebo

RCT
Phase 2-3
Children (>=12Y yo), adolescentes and adults, with no history or SARS-CoV 2 infection at 152 sites in Argentina, Brazil, Germany, South Africa, Turkey and USA N=44165 Variant beta:

Some concerns
Details

Full description

Delta
CTRI/2021/08/036074
Biological E;AstraZeneca+University of Oxford
Thuluva , medRxiv, 2022

Full text
Commentary
Commentary
Protein subunit

BECOV2

ChAdOx1

RCT
Phase 3
Healthy adults without a history of Covid-19 vaccination or SARS-CoV-2 infection at 20 centers in India. N=2140
Some concerns
Details

Full description

Delta
CTRI/2021/10/037066
Biological E. Limited
Thuluva , medRxiv, 2022

Full text
Commentary
Commentary
Protein subunit

BECOV2<12 to ≥5

BECOV2<18 to ≥12

Placebo

RCT
Phase 2-3
Healthy children and adolescents who were SARS-CoV-2 RT-PCR and anti-SARS-CoV-2 antibody negative in 23 centers in India N=624
Low
Details

Full description

Alpha
Beta
Delta
RPCEC00000347
Instituto Finlay de Vacunas
Toledo-Romani ME, medRxiv, 2022

Full text
Commentary
Commentary
Protein subunit

SOBERANA 02/SOBERANA plus

Adjuvant

RCT
Phase 2b
Healthy adults with no known or suspected history of COVID-19 at 2 centers in Cuba. N=810
Some concerns
Details

Full description

Alpha
Beta
Delta
NCT04471519
Bharat Biotech
Vadrevu KM, medRxiv, 2022

Full text
Commentary
Commentary
Inactivated virus

BBV152/Boost

Placebo

RCT
Phase 2
Adolescents and adults aged 12-64 years with no history of confirmed COVID-19, who had received a 2-dose schedule of the same vaccine 6 months previously at 9 centers in India. N=184
Some concerns
Details

Full description