Antibody Response of Heterologous vs Homologous mRNA Vaccine Boosters Against the SARS-CoV-2 Omicron Variant: Interim Results from the PRIBIVAC Study, A Randomized Clinical Trial

35 Pages Posted: 16 Mar 2022

See all articles by Xuan Ying Poh

Xuan Ying Poh

National Centre for Infectious Diseases

Chee Wah Tan

Duke NUS Medical School

I. Russel Lee

National Centre for Infectious Diseases

Jean-Marc Chavatte

National Centre for Infectious Diseases

Siew‐Wai Fong

Agency for Science, Technology and Research (A*STAR) - A*STAR Infectious Diseases Labs

Tessa Prince

University of Liverpool

Catherine Hartley

University of Liverpool

Aileen Ying-Yan Yeoh

Duke-NUS Medical School

Suma Rao

National Centre for Infectious Diseases

Po Ying Chia

National Centre for Infectious Diseases

Sean Wei Xiang Ong

National Centre for Infectious Diseases, Singapore

Tau Hong Lee

National Centre for Infectious Diseases, Singapore

Sapna P. Sadarangani

National Centre for Infectious Diseases

Ray JH Lin

National Centre for Infectious Diseases

Clarissa Lim

National Centre for Infectious Diseases

Jefanie Teo

National Centre for Infectious Diseases

Daniel WX Lim

National Centre for Infectious Diseases

Wanni Chia

Duke-NUS Medical School

Julian A. Hiscox

University of Liverpool

Lisa F.P. Ng

Agency for Science, Technology and Research (A*STAR) - A*STAR Infectious Diseases Labs

Ee Chee Ren

National University of Singapore (NUS)

Raymond Tzer Pin Lin

National Centre for Infectious Diseases

Laurent Renia

Agency for Science, Technology and Research (A*STAR) - A*STAR Infectious Diseases Labs

David Chien Lye

Nanyang Technological University (NTU) - Lee Kong Chian School of Medicine; National University of Singapore (NUS) - Department of Microbiology and Immunology

Lin Fa Wang

Duke-NUS Medical School - Programme in Emerging Infectious Diseases

Barnaby E. Young

National Centre for Infectious Diseases, Singapore

Date Written: February 17, 2022

Abstract

Background: Waning antibody levels post-vaccination and the emergence of variants of concern (VOCs) capable of evading protective immunity has raised the need for booster vaccinations. However, which combination of COVID-19 vaccines offers the strongest immune response against Omicron variant is unknown.

Methods: This randomized, subject-blinded, controlled trial assess the reactogenicity and immunogenicity of different COVID-19 vaccine booster combinations. 100 BNT162b2-vaccinated individuals were enrolled and randomized 1:1 to either homologous (BNT162b2+BNT162b2+BNT162b2; ‘BBB’) or heterologous mRNA booster vaccine (BNT162b2+BNT162b2+mRNA-1273; ‘BBM’). Primary endpoint was the level of neutralizing antibodies against SARS-CoV-2 wild-type and VOCs at Day 28.

Results: 51 participants were allocated to BBB and 49 to BBM; 50 and 48 respectively were analyzed for safety and immunogenicity outcomes. At Day 28 post-boost, mean SARS-CoV-2 spike antibody titers were lower with BBB (22,382 IU/mL 95% CI, 18,210 to 27,517) vs BBM (29,751 IU/mL 95% CI, 25,281 to 35,011, p=0·034) as was the median level of neutralizing antibodies: BBB 99.0% (IQR 97·9 to 99·3%) vs BBM 99.3% (IQR 98·8 to 99·5%, p=0·021). On sub-group analysis, significant differences in mean spike antibody titer and live Omicron neutralization titer was only observed in older adults. Median surrogate neutralizing antibody level against all VOCs was also significantly higher with BBM in older adults, and against Omicron was BBB 72·8% (IQR 54·0 to 84·7%) vs BBM 84·3% (IQR 78·1 to 88·7%, p=0·0073). Both vaccines were well tolerated.
Conclusions: Heterologous mRNA-1273 booster vaccination induced a stronger neutralizing response against the Omicron variant in older individuals compared with homologous BNT123b2.

Note:
Funding Information: The study is supported in part by grants from Singapore National Medical Research Council [STPRG-FY19-001, COVID19RF-003, COVID19RF-011, COVID19RF-018, COVID19RF-060 and OFLCG19May-0034]. This live virus inhibition work was partially funded by the US Food and Drug Administration Medical Countermeasures Initiative contract (75F40120C00085). This work was also supported by the Medical Research Council [MR/W005611/1 to J.A.H.] G2P-UK: A national virology consortium to address phenotypic consequences of SARS-CoV- 2 genomic variation.

Conflict of Interests: Young reports personal fees from Astra-Zeneca, Gilead, Roche, Sanofi and Novacyte outside the submitted work. All other authors no potential conflicts of interest.

Ethical Approval: Written informed consent was obtained from all study participants. Ethical approval from National Healthcare Group Domain Specific Review Board (NHG DSRB, study reference 2021/00821).

Trial Registration: The study was registered with ClinicalTrials.gov (NCT05142319).

Keywords: COVID-19 vaccine booster, humoral immunity, omicron, live virus neutralization

JEL Classification: I18

Suggested Citation

Poh, Xuan Ying and Tan, Chee Wah and Lee, I. Russel and Chavatte, Jean-Marc and Fong, Siew‐Wai and Prince, Tessa and Hartley, Catherine and Yeoh, Aileen Ying-Yan and Rao, Suma and Chia, Po Ying and Ong, Sean Wei Xiang and Lee, Tau Hong and Sadarangani, Sapna P. and Lin, Ray JH and Lim, Clarissa and Teo, Jefanie and Lim, Daniel WX and Chia, Wanni and Hiscox, Julian A. and Ng, Lisa F.P. and Ren, Ee Chee and Lin, Raymond Tzer Pin and Renia, Laurent and Lye, David Chien and Wang, Lin Fa and Young, Barnaby E., Antibody Response of Heterologous vs Homologous mRNA Vaccine Boosters Against the SARS-CoV-2 Omicron Variant: Interim Results from the PRIBIVAC Study, A Randomized Clinical Trial (February 17, 2022). Available at SSRN: https://ssrn.com/abstract=4056669 or http://dx.doi.org/10.2139/ssrn.4056669

Xuan Ying Poh

National Centre for Infectious Diseases ( email )

16 Jln Tan Tock Seng
308442
Singapore

Chee Wah Tan

Duke NUS Medical School

Singapore

I. Russel Lee

National Centre for Infectious Diseases ( email )

Singapore

Jean-Marc Chavatte

National Centre for Infectious Diseases ( email )

Singapore

Siew‐Wai Fong

Agency for Science, Technology and Research (A*STAR) - A*STAR Infectious Diseases Labs ( email )

Singapore

Tessa Prince

University of Liverpool ( email )

Chatham Street
Liverpool, L69 7ZA
United Kingdom

Catherine Hartley

University of Liverpool ( email )

Chatham Street
Liverpool, L69 7ZA
United Kingdom

Aileen Ying-Yan Yeoh

Duke-NUS Medical School ( email )

8 College Road
Singapore, 169857
Singapore

Suma Rao

National Centre for Infectious Diseases ( email )

Singapore

Po Ying Chia

National Centre for Infectious Diseases ( email )

Singapore

Sean Wei Xiang Ong

National Centre for Infectious Diseases, Singapore

Singapore

Tau Hong Lee

National Centre for Infectious Diseases, Singapore

Singapore

Sapna P. Sadarangani

National Centre for Infectious Diseases

Singapore

Ray JH Lin

National Centre for Infectious Diseases ( email )

Singapore

Clarissa Lim

National Centre for Infectious Diseases ( email )

Singapore

Jefanie Teo

National Centre for Infectious Diseases ( email )

Singapore

Daniel WX Lim

National Centre for Infectious Diseases ( email )

Singapore

Wanni Chia

Duke-NUS Medical School ( email )

8 College Road
Singapore, 169857
Singapore

Julian A. Hiscox

University of Liverpool ( email )

Chatham Street
Liverpool, L69 7ZA
United Kingdom

Lisa F.P. Ng

Agency for Science, Technology and Research (A*STAR) - A*STAR Infectious Diseases Labs ( email )

Singapore

Ee Chee Ren

National University of Singapore (NUS) ( email )

1E Kent Ridge Road
NUHS Tower Block Level 7
Singapore, 119228
Singapore

Raymond Tzer Pin Lin

National Centre for Infectious Diseases ( email )

Laurent Renia

Agency for Science, Technology and Research (A*STAR) - A*STAR Infectious Diseases Labs ( email )

Singapore

David Chien Lye

Nanyang Technological University (NTU) - Lee Kong Chian School of Medicine ( email )

National University of Singapore (NUS) - Department of Microbiology and Immunology ( email )

5 Science Drive 2 Blk MD4, Level 3
117545
Singapore

Lin Fa Wang

Duke-NUS Medical School - Programme in Emerging Infectious Diseases ( email )

Singapore

Barnaby E. Young (Contact Author)

National Centre for Infectious Diseases, Singapore ( email )

Singapore

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