Hybrid immunity shifts the Fc-effector quality of SARS-CoV-2 mRNA vaccine-induced immunity

Bowman, K. A.; Stein, D.; Shin, S.; Ferbas, K. G.; Tobin, N.; Mann, C.; Fischinger, S.; Ollmann Saphire, E.; Lauffenberger, D.; Rimoin, A.; Aldrovandi, G.; Alter, G.

doi:10.1101/2022.06.10.495727

bioRxiv · 10.1101/2022.06.10.495727

Hybrid immunity shifts the Fc-effector quality of SARS-CoV-2 mRNA vaccine-induced immunity

Bowman, K. A.·Stein, D.·Shin, S.·Ferbas, K. G.·Tobin, N.·Mann, C.·Fischinger, S.·Ollmann Saphire, E.·Lauffenberger, D.·Rimoin, A.·Aldrovandi, G.·Alter, G.

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Abstract

Despite the robust immunogenicity of SARS-CoV-2 mRNA vaccines, emerging data reveal enhanced neutralizing antibody and T cell cross-reactivity among individuals that previously experienced COVID-19, pointing to a hybrid immune advantage with infection-associated immune priming. Beyond neutralizing antibodies and T cell immunity, mounting data point to a potential role for additional antibody effector functions, including opsinophagocytic activity, in the resolution of symptomatic COVID-19. Whether hybrid immunity modifies the Fc-effector profile of the mRNA vaccine-induced immune response remains incompletely understood. Thus, here we profiled the SARS-CoV-2 specific humoral immune response in a group of individuals with and without prior COVID-19. As expected, hybrid Spike-specific antibody titers were enhanced following the primary dose of the mRNA vaccine, but were similar to those achieved by naive vaccinees after the second mRNA vaccine dose. Conversely, Spike-specific vaccine-induced Fc-receptor binding antibody levels were higher after the primary immunization in individuals with prior COVID-19, and remained higher following the second dose compared to naive individuals, suggestive of a selective improvement in the quality, rather than the quantity, of the hybrid humoral immune response. Thus, while the magnitude of antibody titers alone may suggest that any two antigen exposures - either hybrid immunity or two doses of vaccine alone - represent a comparable prime/boost immunologic education, we find that hybrid immunity offers a qualitatively improved antibody response able to better leverage Fc effector functions against conserved regions of the virus.

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Bowman, K. A., Stein, D., Shin, S., Ferbas, K. G., Tobin, N., Mann, C., Fischinger, S., Ollmann Saphire, E., Lauffenberger, D., Rimoin, A., Aldrovandi, G., Alter, G.. 2022-06-11. Hybrid immunity shifts the Fc-effector quality of SARS-CoV-2 mRNA vaccine-induced immunity. https://doi.org/10.1101/2022.06.10.495727

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