The effect of single mutations in Zika virus envelope on escape from broadly neutralizing antibodies.

Autor:	Kikawa C; Department of Genome Sciences, University of Washington , Seattle, Washington, USA.; Medical Scientist Training Program, University of Washington , Seattle, Washington, USA.; Vaccine and Infectious Disease Division, Fred Hutch Cancer Center , Seattle, Washington, USA., Cartwright-Acar CH; Vaccine and Infectious Disease Division, Fred Hutch Cancer Center , Seattle, Washington, USA., Stuart JB; Vaccine and Infectious Disease Division, Fred Hutch Cancer Center , Seattle, Washington, USA., Contreras M; Vaccine and Infectious Disease Division, Fred Hutch Cancer Center , Seattle, Washington, USA., Levoir LM; Vaccine and Infectious Disease Division, Fred Hutch Cancer Center , Seattle, Washington, USA., Evans MJ; Department of Microbiology, Icahn School of Medicine at Mount Sinai , New York, New York, USA., Bloom JD; Department of Genome Sciences, University of Washington , Seattle, Washington, USA.; Basic Sciences, Fred Hutch Cancer Center , Seattle, Washington, USA.; Computational Biology, Fred Hutch Cancer Center , Seattle, Washington, USA.; Howard Hughes Medical Institute , Seattle, Washington, USA., Goo L; Vaccine and Infectious Disease Division, Fred Hutch Cancer Center , Seattle, Washington, USA.
Jazyk:	angličtina
Zdroj:	Journal of virology [J Virol] 2023 Nov 30; Vol. 97 (11), pp. e0141423. Date of Electronic Publication: 2023 Nov 09.
DOI:	10.1128/jvi.01414-23
Abstrakt:	Importance: The wide endemic range of mosquito-vectored flaviviruses-such as Zika virus and dengue virus serotypes 1-4-places hundreds of millions of people at risk of infection every year. Despite this, there are no widely available vaccines, and treatment of severe cases is limited to supportive care. An avenue toward development of more widely applicable vaccines and targeted therapies is the characterization of monoclonal antibodies that broadly neutralize all these viruses. Here, we measure how single amino acid mutations in viral envelope protein affect neutralizing antibodies with both broad and narrow specificities. We find that broadly neutralizing antibodies with potential as vaccine prototypes or biological therapeutics are quantifiably more difficult to escape than narrow, virus-specific neutralizing antibodies. Competing Interests: J.D.B. is on the scientific advisory boards of Apriori Bio, Invivyd, Aerium Therapeutics, and the Vaccine Company and receives royalty payments as an inventor on Fred Hutch licensed patents related to viral deep mutational scanning. J.B.S. is currently an employee of Universal Cells but performed all work included in this manuscript while an employee of Fred Hutch Cancer Center.
Databáze:	MEDLINE
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