8VIA

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

Summary for 8VIA

• Entry DOI: 10.2210/pdb8via/pdb
• EMDB information: 43255
• Descriptor: Spike protein S1, Spike protein S2, PVI.V5-4 heavy chain, ... (6 entities in total)
• Functional Keywords: antibody, sars-cov-2, spike, immune system
• Biological source: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV, SARS-CoV-2); More
• Total number of polymer chains: 4
• Total formula weight: 186380.60

Authors

Bajic, G. (deposition date: 2024-01-03, release date: 2024-10-23, Last modification date: 2024-11-27)

Primary citation

Clark, J.J.,Hoxie, I.,Adelsberg, D.C.,Sapse, I.A.,Andreata-Santos, R.,Yong, J.S.,Amanat, F.,Tcheou, J.,Raskin, A.,Singh, G.,Gonzalez-Dominguez, I.,Edgar, J.E.,Bournazos, S.,Sun, W.,Carreno, J.M.,Simon, V.,Ellebedy, A.H.,Bajic, G.,Krammer, F.
Protective effect and molecular mechanisms of human non-neutralizing cross-reactive spike antibodies elicited by SARS-CoV-2 mRNA vaccination.
Cell Rep, 43:114922-114922, 2024

PubMed 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.

PubMed: 39504245
DOI: 10.1016/j.celrep.2024.114922

Experimental method

ELECTRON MICROSCOPY (3.6 Å)