Antibodies to S2 domain of SARS-CoV-2 spike protein in Moderna mRNA vaccinated subjects sustain antibody-dependent NK cell-mediated cell cytotoxicity against Omicron BA.1.

Autor:	Balinsky CA; Henry Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, United States., Jiang L; Henry Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, United States., Jani V; Henry Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, United States., Cheng Y; Leidos, Reston, VA, United States., Zhang Z; Henry Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, United States., Belinskaya T; Henry Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, United States., Qiu Q; Henry Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, United States., Long TK; Vysnova Partners, Inc., Landover, MD, United States., Schilling MA; Virology and Emerging Infectious Department, U.S. Naval Medical Research Unit SOUTH, Lima, Peru., Jenkins SA; Diagnostics and Surveillance Department, Naval Medical Research Command, Silver Spring, MD, United States., Corson KS; US Naval Medical Research Unit-INDO PACIFIC, Singapore, Singapore., Martin NJ; U.S. Naval Medical Research Unit Eurafcent, Sigonella, Italy., Letizia AG; US Naval Medical Research Unit-INDO PACIFIC, Singapore, Singapore., Hontz RD; US Naval Medical Research Unit-INDO PACIFIC, Singapore, Singapore., Sun P; Diagnostics and Surveillance Department, Naval Medical Research Command, Silver Spring, MD, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2023 Nov 21; Vol. 14, pp. 1266829. Date of Electronic Publication: 2023 Nov 21 (Print Publication: 2023).
DOI:	10.3389/fimmu.2023.1266829
Abstrakt:	Vaccination with the primary two-dose series of SARS-CoV-2 mRNA protects against infection with the ancestral strain, and limits the presentation of severe disease after re-infection by multiple variants of concern (VOC), including Omicron, despite the lack of a strong neutralizing response to these variants. We compared antibody responses in serum samples collected from mRNA-1273 (Moderna) vaccinated subjects to identify mechanisms of immune escape and cross-protection. Using pseudovirus constructs containing domain-specific amino acid changes representative of Omicron BA.1, combined with domain competition and RBD-antibody depletion, we showed that RBD antibodies were primarily responsible for virus neutralization and variant escape. Antibodies to NTD played a less significant role in antibody neutralization but acted along with RBD to enhance neutralization. S2 of Omicron BA.1 had no impact on neutralization escape, suggesting it is a less critical domain for antibody neutralization; however, it was as capable as S1 at eliciting IgG3 responses and NK-cell mediated, antibody-dependent cell cytotoxicity (ADCC). Antibody neutralization and ADCC activities to RBD, NTD, and S1 were all prone to BA.1 escape. In contrast, ADCC activities to S2 resisted BA.1 escape. In conclusion, S2 antibodies showed potent ADCC function and resisted Omicron BA.1 escape, suggesting that S2 contributes to cross-protection against Omicron BA.1. In line with its conserved nature, S2 may hold promise as a vaccine target against future variants of SARS-CoV-2. Competing Interests: Author YC was employed by the company Leidos. Author TL was employed by company Vysnova Partners, Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Balinsky, Jiang, Jani, Cheng, Zhang, Belinskaya, Qiu, Long, Schilling, Jenkins, Corson, Martin, Letizia, Hontz and Sun.)
Databáze:	MEDLINE
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