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

• Published in: Cell reports. Medicine Vol. 3; no. 5; p. 100631
• Main Authors: Takano, Tomohiro, Morikawa, Miwa, Adachi, Yu, Kabasawa, Kiyomi, Sax, Nicolas, Moriyama, Saya, Sun, Lin, Isogawa, Masanori, Nishiyama, Ayae, Onodera, Taishi, Terahara, Kazutaka, Tonouchi, Keisuke, Nishimura, Masashi, Tomii, Kentaro, Yamashita, Kazuo, Matsumura, Takayuki, Shinkai, Masaharu, Takahashi, Yoshimasa
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 17.05.2022; Elsevier
• Subjects: Advanced Basic Science; adverse events; Antibodies, Neutralizing - immunology; Antibodies, Viral - immunology; BNT162 Vaccine - adverse effects; BNT162 Vaccine - immunology; BNT162 Vaccine - therapeutic use; cell dynamics; COVID-19 - immunology; COVID-19 - prevention & control; COVID-19 Vaccines - adverse effects; COVID-19 Vaccines - immunology; COVID-19 Vaccines - therapeutic use; Humans; immune correlates; innate immunity; mRNA vaccine; mRNA Vaccines - adverse effects; mRNA Vaccines - immunology; mRNA Vaccines - therapeutic use; neutralizing antibodies; SARS-CoV-2; SARS-CoV-2 - genetics; Vaccines, Synthetic - adverse effects; Vaccines, Synthetic - immunology; Vaccines, Synthetic - therapeutic use; SARS-CoV-2; immune correlates; innate immunity; neutralizing antibodies; adverse events; mRNA vaccine; cell dynamics
• ISSN: 2666-3791; 2666-3791
• DOI: 10.1016/j.xcrm.2022.100631

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. [Display omitted] •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 Takano et al. identify cellular correlates for neutralizing-antibody titers and systemic adverse events following SARS-CoV-2 mRNA vaccination. The involvement of IFN-γ-mediated pathways is proposed. The findings give insights into balancing the immunogenicity and reactogenicity of mRNA vaccine.