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
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 Variant delta:

Some concerns
Details

Full description

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

NCT05087368
Clover Biopharmaceuticals Inc./Dynavax ; AstraZeneca + University of Oxford
Costa Clemens, Open Forum Infect. Dis., 2022

Full text
Commentary
Commentary
Commentary
Commentary
Protein subunit

ChAd/boost9mcgSCB-2019+al

ChAd/B*9SCB-2019+al+CpG

ChAd/B*30SCB-2019+al+CpG

ChadOx1/boostChadOx1

RCT
Phase 2
Adults including healthy or stable co-morbidities with no history of SARS-CoV-2 infection who had previously received 2 doses of ChAdOx1-S1-S vaccine 6 months (±4 weeks) before enrollment in 3 centers in Brazil N=120
Some concerns
Details

Full description

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

Delta
NCT04796896
ModernaTX
Creech CB, N Engl J Med, 2022
KidCOVE

Full text
Commentary
RNA based vaccine

mRNA-1273 (50 mcg)

Placebo

RCT
Phase 2-3
Children aged 6-11 years, healthy or with stable chronic conditions and no known recent history of COVID-19 infection, at 87 centers in Canada and USA. N=4016 Variant delta:

Some concerns
Details

Full description

Alpha
Gamma
Delta
NCT04646590
Anhui Zhifei Longcom Biopharmaceutical
Dai L, N Engl J Med, 2022

Full text
Commentary
Commentary
Protein subunit

ZF2001

Placebo

RCT
Phase 3
Adults 18 years of age or older with no history of Covid-19, positive tests for SARS-CoV-2 exposure or vaccination, or of congenital or acquired immune deficiency or autoimmune disease at 32 clinical centers across Uzbekistan, Indonesia, Pakistan, Ecuador and China. N=28904 Variant delta:

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

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 Variant delta:

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
NCT04614948
Janssen Pharmaceutical Companies
Hardt K, Lancet Infect Dis, 2022
ENSEMBLE2

Full text
Full text
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
Beta
Gamma
Delta
NCT04614948
Janssen Pharmaceutical Companies
Hardt K, Lancet Infect Dis, 2022
ENSEMBLE2

Full text
Full text
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
NCT04583995; EudraCT 2020-004123-16
Novavax
Heath P, Clin Infect Dis, 2022

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=15185 Variant alpha:

Some concerns
Details

Full description

Beta
RPCEC00000359
Center for Genetic Engineering and Biotechnology (CIGB)
Hernandez-Bernal F, SSRN, 2022
Abdala-3

Full text
Commentary
Commentary
Commentary
Protein subunit

Abdala

Placebo

RCT
Phase 3
Adults, healthy or with controlled co-morbidities and no history of SARS-CoV-2 at 18 centers in Cuba N=48290
Some concerns
Details

Full description

Alpha
Beta
Delta
NCT04649021
Pfizer/BioNTech+Fosun Pharma
Hui A-M, Lancet, 2022

Full text
Full text
Commentary
Commentary
RNA based vaccine

BNT162b2

Placebo

RCT
Phase 2
Healthy adults and those with a pre-existing stable condition, at 2 centers in China. N=960
Low
Details

Full description

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
Phase 1
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

Delta
CTRI/2021/01/030416
Zydus Cadila
Khobragade A, Lancet , 2022

Full text
Commentary
DNA based vaccine

ZyCoV-D

Placebo

RCT
Phase 3
Healthy adults and adolescents aged (≥12 years) with no previous history of COVID-19 at 49 centers in India. N=27703 Variant delta:

Some concerns
Details

Full description

Beta
Delta
NCT04444674
AstraZeneca + University of Oxford
Koen A, medRxiv, 2022
COV005

Full text
Full text
Commentary
Non replicating viral vector

ChAdOx1

Placebo

RCT
Phase 1-2
Healthy adults aged 18–65 years in 7 centres in South Africa N=2130 Variant beta:

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

EudraCT, 2022-000063-51; NCT05249829
ModernaTX/National Institute of Allergy and Infectious Diseases (NIAID)
Lee l, medRxiv, 2023

Full text
Commentary
Commentary
Heterologous booster

2nd Boost mRNA-1273.214

2nd Boost mRNA-1273

RCT
Phase 2-3
Healthy or stable co-morbidities, at least 16 years who had previously received 2 injections of an authorized Covid-19 primary series vaccine with or without an mRNA-based booster as the third dose in 28 centres in UK. N=2824
Some concerns
Details

Full description

Beta
NCT04533399; PACTR202009726132275
Novavax
Madhi S, Lancet HIV, 2022

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=4419 Variant beta:

Some concerns
Details

Full description

NCT04368988
Novavax
Mallory R, Lancet Infect Dis, 2022

Full text
Full text
Commentary
Commentary
Protein subunit

NVX-CoV2373 boost

NVX-CoV2373

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

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

Full text
Commentary
RNA based vaccine

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

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

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

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

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

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

ChadOx1/boostNVX(half)

ChadOx1/boostNVX(half)

ChadOx1/Placebo

ChadOx1/Placebo

ChadOx1/boost

ChadOx1/boost

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

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

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

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 Variant delta:

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

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

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

Full text
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
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 S, Vaccine, 2022

Full text
Full text
Commentary
Commentary
Commentary
Protein subunit

BECOV2 ≥5 to <12

BECOV2 ≥12 to <18

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=390
Low
Details

Full description

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

Full text
Commentary
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

NCT04471519; CTRI/2021/04/032942
Bharat Biotech
Vadrevu KM, Sci Rep, 2022

Full text
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

Delta
NCT04816643
Pfizer/BioNTech+Fosun Pharma
Walter E, N Engl J Med, 2021

Full text
Commentary
RNA based vaccine

BNT162b2 10 mcg

Placebo

RCT
Phase 2-3
Children aged 5-11 years with or without stable co-morbidities with no history of COVID-19 in 81 centres in the USA, Spain, Finland, and Poland N=2285 Variant delta:

Some concerns
Details

Full description

ChiCTR2100051391
Beijing Wantai Biological Pharmacy Enterprise Co., Ltd.
Xia N, Research Square, 2023

Full text
Commentary
Heterologous booster

Any prime/Boost dNS1-RBD

Any prime/Boost placebo

RCT
Phase 3
Adultsincluding healthy and mild stable co-morbidities without prior COVID-19 history in 33 centres in Philippines, South Africa, Colombia and Vietnam N=17210
Some concerns
Details

Full description