Antibody Response of Heterologous vs Homologous Messenger RNA Vaccine Boosters Against the Severe Acute Respiratory Syndrome Coronavirus 2 Omicron Variant: Interim Results from the PRIBIVAC Study, a Randomized Clinical Trial.
Xuan Ying Poh, Chee Wah Tan, I Russel Lee, Jean-Marc Chavatte, Siew-Wai Fong, Tessa Prince, Catherine Hartley, Aileen Y Y Yeoh, Suma Rao, Po Ying Chia, Sean W X Ong, Tau Hong Lee, Sapna P Sadarangani, Ray J H Lin, Clarissa Lim, Jefanie Teo, Daniel R X Lim, Wanni Chia, Julian A Hiscox, Lisa F P Ng, Ee Chee Ren, Raymond T P Lin, Laurent Renia, David Chien Lye, Lin-Fa Wang, Barnaby E Young
Author Information
Xuan Ying Poh: National Centre for Infectious Diseases, Singapore, Singapore. ORCID
Chee Wah Tan: Emerging Infectious Diseases Programme, Duke-National University of Singapore Medical School, Singapore, Singapore.
I Russel Lee: National Centre for Infectious Diseases, Singapore, Singapore.
Jean-Marc Chavatte: National Centre for Infectious Diseases, Singapore, Singapore.
Siew-Wai Fong: A*STAR Infectious Diseases Lab, Agency for Science Technology and Research, Singapore, Singapore.
Tessa Prince: Department of Infection Biology, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, United Kingdom.
Catherine Hartley: Department of Infection Biology, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, United Kingdom.
Aileen Y Y Yeoh: Emerging Infectious Diseases Programme, Duke-National University of Singapore Medical School, Singapore, Singapore.
Suma Rao: National Centre for Infectious Diseases, Singapore, Singapore.
Po Ying Chia: National Centre for Infectious Diseases, Singapore, Singapore.
Sean W X 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, Singapore.
Ray J H Lin: National Centre for Infectious Diseases, Singapore, Singapore.
Clarissa Lim: National Centre for Infectious Diseases, Singapore, Singapore.
Jefanie Teo: National Centre for Infectious Diseases, Singapore, Singapore.
Daniel R X Lim: National Centre for Infectious Diseases, Singapore, Singapore.
Wanni Chia: Emerging Infectious Diseases Programme, Duke-National University of Singapore Medical School, Singapore, Singapore.
Julian A Hiscox: A*STAR Infectious Diseases Lab, Agency for Science Technology and Research, Singapore, Singapore.
Lisa F P Ng: A*STAR Infectious Diseases Lab, Agency for Science Technology and Research, Singapore, Singapore.
Ee Chee Ren: Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Raymond T P Lin: National Centre for Infectious Diseases, Singapore, Singapore.
Laurent Renia: A*STAR Infectious Diseases Lab, Agency for Science Technology and Research, Singapore, Singapore.
David Chien Lye: National Centre for Infectious Diseases, Singapore, Singapore.
Lin-Fa Wang: Emerging Infectious Diseases Programme, Duke-National University of Singapore Medical School, Singapore, Singapore.
Barnaby E Young: National Centre for Infectious Diseases, Singapore, Singapore.
BACKGROUND: Waning antibody levels post-vaccination and the emergence of variants of concern (VOCs) capable of evading protective immunity have raised the need for booster vaccinations. However, which combination of coronavirus disease 2019 (COVID-19) vaccines offers the strongest immune response against the Omicron variant is unknown. METHODS: This randomized, participant-blinded, controlled trial assessed the reactogenicity and immunogenicity of different COVID-19 vaccine booster combinations. A total of 100 BNT162b2-vaccinated individuals were enrolled and randomized 1:1 to either homologous (BNT162b2 + BNT162b2 + BNT162b2; "BBB") or heterologous messenger RNA (mRNA) (BNT162b2 + BNT162b2 + mRNA-1273; "BBM") booster vaccine. The primary end point was the level of neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) wild-type and VOCs at day 28. RESULTS: A total of 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% confidence interval [CI], 18 210 to 27 517) vs BBM (29 751 IU/mL; 95% CI, 25 281 to 35 011; P = .034) as was the median level of neutralizing antibodies: BBB 99.0% (interquartile range [IQR], 97.9% to 99.3%) vs BBM 99.3% (IQR, 98.8% to 99.5%; P = .021). On subgroup analysis, significant higher mean spike antibody titer, median surrogate neutralizing antibody level against all VOCs, and live Omicron neutralization titer were observed only in older adults receiving BBM. Both vaccines were well tolerated. CONCLUSIONS: Heterologous mRNA-1273 booster vaccination compared with homologous BNT123b2 induced a stronger neutralizing response against the Omicron variant in older individuals. CLINICAL TRIALS REGISTRATION: NCT05142319.
