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In Cell reports. Medicine

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.

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

2022-Apr-22

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