Antibody Fc receptor binding and T cell responses to homologous and heterologous immunization with inactivated or mRNA vaccines against SARS-CoV-2

Carolyn A. Cohen, Nancy H. L. Leung, Prathanporn Kaewpreedee, Kelly W. K. Lee, Janice Zhirong Jia, Alan W. L. Cheung, Samuel M. S. Cheng, Masashi Mori, Dennis K. M. Ip, Leo L. M. Poon, J. S. Malik Peiris, Benjamin J. Cowling and Sophie A. Valkenburg ()
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Carolyn A. Cohen: The University of Hong Kong
Nancy H. L. Leung: The University of Hong Kong
Prathanporn Kaewpreedee: The University of Hong Kong
Kelly W. K. Lee: The University of Hong Kong
Janice Zhirong Jia: The University of Hong Kong
Alan W. L. Cheung: The University of Hong Kong
Samuel M. S. Cheng: The University of Hong Kong
Masashi Mori: Ishikawa Prefectural University
Dennis K. M. Ip: The University of Hong Kong
Leo L. M. Poon: The University of Hong Kong
J. S. Malik Peiris: The University of Hong Kong
Benjamin J. Cowling: The University of Hong Kong
Sophie A. Valkenburg: The University of Hong Kong

Nature Communications, 2024, vol. 15, issue 1, 1-15

Abstract: Abstract Whole virion inactivated vaccine CoronaVac (C) and Spike (S) mRNA BNT162b2 (B) vaccines differ greatly in their ability to elicit neutralizing antibodies but have somewhat comparable effectiveness in protecting from severe COVID-19. We conducted further analyses for a randomized trial (Cobovax study, NCT05057169) of third dose homologous and heterologous booster vaccination, i.e. four interventions CC-C, CC-B, BB-C and BB-B. Here, we assess vaccine immunogenicity beyond neutralizing function, including S and non-S antibodies with Fc receptor (FcR) binding, antibody avidity and T cell specificity to 6 months post-vaccination. Ancestral and Omicron S-specific IgG and FcR binding are significantly higher by BNT162b2 booster than CoronaVac, regardless of first doses. Nucleocapsid (N) antibodies are only increased in homologous boosted CoronaVac participants (CC-C). CoronaVac primed participants have lower baseline S-specific CD4+ IFNγ+ cells, but are significantly increased by either CoronaVac or BNT162b2 boosters. Priming vaccine content defined T cell peptide specificity preference, with S-specific T cells dominating B primed groups and non-S structural peptides contributing more in C primed groups, regardless of booster type. S-specific CD4+ T cell responses, N-specific antibodies, and antibody effector functions via Fc receptor binding may contribute to protection and compensate for less potent neutralizing responses in CoronaVac recipients.

Date: 2024
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DOI: 10.1038/s41467-024-51427-1

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