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

https://doi.org/10.1016/j.xcrm.2022.100631Get rights and content
Under a Creative Commons license
open access

Highlights

  • Immune profiling of mRNA vaccinees reveals dramatic immunological changes

  • The dynamics of NK/monocyte subsets correlate with neutralizing-antibody response

  • The dynamics of dendritic cell subsets correlate with severity of adverse events

  • IFN-γ-inducible chemokines, but not the receptors, are related to these correlates

Summary

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, CD56high 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.

Keywords

mRNA vaccine
SARS-CoV-2
neutralizing antibodies
adverse events
cell dynamics
immune correlates
innate immunity

Data and code availability

All data reported in this paper will be shared by the lead contact upon request. This paper does not report the original code. Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.

Cited by (0)

6

These authors contributed equally

7

Lead contact