Protective effect and molecular mechanisms of human non-neutralizing cross-reactive spike antibodies elicited by SARS-CoV-2 mRNA vaccination

Author(s):Show less -

Clark, Jordan J. ; Hoxie, Irene ; Adelsberg, Daniel C. ; Sapse, Iden A. ; Andreata-Santos, Robert ; Yong, Jeremy S. ; Amanat, Fatima ; Tcheou, Johnstone ; Raskin, Ariel ; Singh, Gagandeep ; Gonzalez-Dominguez, Irene ; Edgar, Julia E. ; Bournazos, Stylianos ; Sun, Weina ; Carreno, Juan Manuel ; Simon, Viviana ; Ellebedy, Ali H. ; Bajic, Goran ; Krammer, Florian

• Document type: Journal article
• Source: CELL REPORTS; v. 43, n. 11, p. 21-pg., 2024-11-05.

Abstract

Neutralizing antibodies correlate with protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Recent studies, however, show that binding antibody titers, in the absence of robust neutralizing activity, also correlate with protection against disease progression. Non-neutralizing antibodies cannot directly protect against infection but may recruit effector cells and thus contribute to the clearance of infected cells. Additionally, they often bind conserved epitopes across multiple variants. Here, we characterize 42 human monoclonal antibodies (mAbs) from coronavirus disease 2019 (COVID-19)-vaccinated individuals. Most of these antibodies exhibit no neutralizing activity in vitro, but several non-neutralizing antibodies provide protection against lethal challenge with SARS-CoV-2 in different animal models. A subset of those mAbs shows a clear dependence on Fc-mediated effector functions. We have determined the structures of three non-neutralizing antibodies, with two targeting the receptor-binding domain and one that binds the subdomain 1 region. Our data confirm the real-world observation in humans that non-neutralizing antibodies to SARS-CoV-2 can be protective. (AU)

• FAPESP's process: 21/05661-1 - Virological characterization of Brazilian SARS-CoV-2 isolates and their neutralization capabilities by serum from previously infected and/or vaccinated individuals
• Grantee: Robert Andreata Santos
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 23/02345-7 - Evaluation of SARS-CoV-2 escape mutants generated after incubation with antibodies raised by different immunization protocols
• Grantee: Robert Andreata Santos
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• FAPESP's process: 20/08943-5 - Investigation of the hosts' induced elements in response to the immunisation with ChAdOx1 nCOV-19 vaccine in a Phase III Clinical Trial
• Grantee: Luiz Mário Ramos Janini
• Support Opportunities: Research Projects - Thematic Grants