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

Cell Rep Med. 2022 May 17;3(5):100631. doi: 10.1016/j.xcrm.2022.100631. Epub 2022 Apr 22.


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

MeSH terms

  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / immunology
  • BNT162 Vaccine* / adverse effects
  • BNT162 Vaccine* / immunology
  • BNT162 Vaccine* / therapeutic use
  • COVID-19 Vaccines / adverse effects
  • COVID-19 Vaccines / immunology
  • COVID-19 Vaccines / therapeutic use
  • COVID-19* / immunology
  • COVID-19* / prevention & control
  • Humans
  • SARS-CoV-2 / genetics
  • Vaccines, Synthetic / adverse effects
  • Vaccines, Synthetic / immunology
  • Vaccines, Synthetic / therapeutic use
  • mRNA Vaccines / adverse effects
  • mRNA Vaccines / immunology
  • mRNA Vaccines / therapeutic use


  • Antibodies, Neutralizing
  • Antibodies, Viral
  • COVID-19 Vaccines
  • Vaccines, Synthetic
  • mRNA Vaccines
  • BNT162 Vaccine