Distinct Immune Cell Dynamics Correlate with the Immunogenicity and Reactogenicity of SARS-CoV-2 mRNA Vaccine

Two doses of Pfizer/BioNTec BNT162b2 mRNA vaccine elicit robust SARS-CoV-2-neutralizing antibodies with frequent adverse events. Here, by applying a high-dimensional immune profiling on 92 vaccinees, we identified six vaccine-induced immune dynamics that correlated with the amounts of neutralizing antibodies, the severity of adverse events, or both. The early dynamics of natural killer/monocyte subsets and two dendritic cell subsets were revealed as the distinct cell correlates for neutralizing antibody titers and adverse events, respectively. Indeed, the combination of two dendritic cell dynamics classified a subgroup of vaccinees with more severe adverse events but with equivalent antibody titers. Among the six cell dynamics, there were multiple dynamics that varied with gender and age, suggesting the possible linkages with gender/age-dependent responses. The identified immune correlates may pave the way for a rational strategy for optimizing an immune balance between the immunogenicity and reactogenicity of the vaccine. Funding: This work was supported by Japan Agency for Medical Research and Development grant (grant number JP20fk0108534 to T.M. and Y.T.). Declaration of Interests: N.S. is an employee of KOTAI Biotechnologies, Inc. K.Y. is a founder, shareholder and board director of KOTAI Biotechnologies, Inc. All other authors declare they have no competing interests. Ethics Approval Statement: All studies were approved by the Institutional Review Board of the National Institute of Infectious Diseases and Tokyo Shinagawa Hospital (Permit 24 numbers: 1292 and 20-A-33). This study was performed in accordance with the principles of the Declaration of Helsinki. All volunteers provided written informed consent prior to enrollment.