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Broadly neutralizing antibody induction by non-stabilized SARS-CoV-2 Spike mRNA vaccination in nonhuman primates.

Publication ,  Journal Article
Malewana, RD; Stalls, V; May, A; Lu, X; Martinez, DR; Schäfer, A; Li, D; Barr, M; Sutherland, LL; Lee, E; Parks, R; Beck, WE; Newman, A ...
Published in: bioRxiv
December 19, 2023

Immunization with mRNA or viral vectors encoding spike with diproline substitutions (S-2P) has provided protective immunity against severe COVID-19 disease. How immunization with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) spike elicits neutralizing antibodies (nAbs) against difficult-to-neutralize variants of concern (VOCs) remains an area of great interest. Here, we compare immunization of macaques with mRNA vaccines expressing ancestral spike either including or lacking diproline substitutions, and show the diproline substitutions were not required for protection against SARS-CoV-2 challenge or induction of broadly neutralizing B cell lineages. One group of nAbs elicited by the ancestral spike lacking diproline substitutions targeted the outer face of the receptor binding domain (RBD), neutralized all tested SARS-CoV-2 VOCs including Omicron XBB.1.5, but lacked cross-Sarbecovirus neutralization. Structural analysis showed that the macaque broad SARS-CoV-2 VOC nAbs bound to the same epitope as a human broad SARS-CoV-2 VOC nAb, DH1193. Vaccine-induced antibodies that targeted the RBD inner face neutralized multiple Sarbecoviruses, protected mice from bat CoV RsSHC014 challenge, but lacked Omicron variant neutralization. Thus, ancestral SARS-CoV-2 spike lacking proline substitutions encoded by nucleoside-modified mRNA can induce B cell lineages binding to distinct RBD sites that either broadly neutralize animal and human Sarbecoviruses or recent Omicron VOCs.

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Published In

bioRxiv

DOI

EISSN

2692-8205

Publication Date

December 19, 2023

Location

United States
 

Citation

APA
Chicago
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Malewana, R. D., Stalls, V., May, A., Lu, X., Martinez, D. R., Schäfer, A., … Saunders, K. O. (2023). Broadly neutralizing antibody induction by non-stabilized SARS-CoV-2 Spike mRNA vaccination in nonhuman primates. BioRxiv. https://doi.org/10.1101/2023.12.18.572191
Malewana, R Dilshan, Victoria Stalls, Aaron May, Xiaozhi Lu, David R. Martinez, Alexandra Schäfer, Dapeng Li, et al. “Broadly neutralizing antibody induction by non-stabilized SARS-CoV-2 Spike mRNA vaccination in nonhuman primates.BioRxiv, December 19, 2023. https://doi.org/10.1101/2023.12.18.572191.
Malewana RD, Stalls V, May A, Lu X, Martinez DR, Schäfer A, et al. Broadly neutralizing antibody induction by non-stabilized SARS-CoV-2 Spike mRNA vaccination in nonhuman primates. bioRxiv. 2023 Dec 19;
Malewana, R. Dilshan, et al. “Broadly neutralizing antibody induction by non-stabilized SARS-CoV-2 Spike mRNA vaccination in nonhuman primates.BioRxiv, Dec. 2023. Pubmed, doi:10.1101/2023.12.18.572191.
Malewana RD, Stalls V, May A, Lu X, Martinez DR, Schäfer A, Li D, Barr M, Sutherland LL, Lee E, Parks R, Beck WE, Newman A, Bock KW, Minai M, Nagata BM, DeMarco CT, Denny TN, Oguin TH, Rountree W, Wang Y, Mansouri K, Edwards RJ, Sempowski GD, Eaton A, Muramatsu H, Henderson R, Tam Y, Barbosa C, Tang J, Cain DW, Santra S, Moore IN, Andersen H, Lewis MG, Golding H, Seder R, Khurana S, Montefiori DC, Pardi N, Weissman D, Baric RS, Acharya P, Haynes BF, Saunders KO. Broadly neutralizing antibody induction by non-stabilized SARS-CoV-2 Spike mRNA vaccination in nonhuman primates. bioRxiv. 2023 Dec 19;

Published In

bioRxiv

DOI

EISSN

2692-8205

Publication Date

December 19, 2023

Location

United States