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: 2024-11-06)

Primary citation

Clark, 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.
Biorxiv, 2024

PubMed Abstract: Neutralizing antibodies correlate with protection against SARS-CoV-2. Recent studies, however, show that binding antibody titers, in the absence of robust neutralizing activity, also correlate with protection from disease progression. Non-neutralizing antibodies cannot directly protect from infection but may recruit effector cells thus contribute to the clearance of infected cells. Also, they often bind conserved epitopes across multiple variants. We characterized 42 human mAbs from COVID-19 vaccinated individuals. Most of these antibodies exhibited no neutralizing activity but several non-neutralizing antibodies protected against lethal challenge with SARS-CoV-2 in different animal models. A subset of those mAbs showed a clear dependence on Fc-mediated effector functions. We determined the structures of three non-neutralizing antibodies with two targeting the RBD, and one that targeting the SD1 region. Our data confirms the real-world observation in humans that non-neutralizing antibodies to SARS-CoV-2 can be protective.

PubMed: 38464151
DOI: 10.1101/2024.02.28.582613

Experimental method

ELECTRON MICROSCOPY (3.6 Å)