Distinct immune cell dynamics correlate with the immunogenicity and reactogenicity of SARS-CoV-2 mRNA vaccine.

Two doses of Pfizer/BioNTech BNT162b2 mRNA vaccine elicit robust severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-neutralizing antibodies with frequent adverse events. Here, by applying a high-dimensional immune profiling on 92 vaccinees, we identify six vaccine-induced immune dynamics that correlate with the amounts of neutralizing antibodies, the severity of adverse events, or both. The early dynamics of natural killer (NK)/monocyte subsets (CD16 ⁺ NK cells, CD56 ^high NK cells, and non-classical monocytes), dendritic cell (DC) subsets (DC3s and CD11c ^- Axl ⁺ Siglec-6 ⁺ [AS]-DCs), and NKT-like cells are revealed as the distinct cell correlates for neutralizing-antibody titers, severity of adverse events, and both, respectively. The cell correlates for neutralizing antibodies or adverse events are consistently associated with elevation of interferon gamma (IFN-γ)-inducible chemokines, but the chemokine receptors CCR2 and CXCR3 are expressed in distinct manners between the two correlates: vaccine-induced expression on the neutralizing-antibody correlate and constitutive expression on the adverse-event correlate. The finding may guide vaccine strategies that balance immunogenicity and reactogenicity.
Competing Interests: 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 that they have no competing interests.
(Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)