Functional, Immunogenetic, and Structural Convergence in Influenza Immunity between Humans and Macaques

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Detalles Bibliográficos
Publicado en:	bioRxiv (Feb 27, 2025)
Autor principal:	Sangesland, Maya
Otros Autores:	Li, Ning, Tsybovsky, Yaroslav, Rodgers, Magan D, Han, Julianna, Rodriguez, Alesandra J, Ferguson, James A, Henry, Amy R, Smith, Sarah C, Roberts-Torres, Jesmine, Gillespie, Rebecca A, Liu, Cuiping, Merriam, Jonah, Stephens, Tyler, Williams, Connor, Maestle, Emma, Corcoran, Martin, Ravichandran, Michelle, Creanga, Adrian, Andrews, Sarah F, Pierson, Theodore C, Karlsson Hedestam, Gunilla B, Schramm, Chaim A, Reed, Douglas S, Douek, Daniel C, Zhou, Tongqing, Ward, Andrew B, Kanekiyo, Masaru
Publicado:	Cold Spring Harbor Laboratory Press
Materias:	Influenza Epitopes Structure-function relationships Immunity Hemagglutinins Immunogenetics
Acceso en línea:	Citation/Abstract Full Text - PDF Full text outside of ProQuest
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Descripción
Resumen:	Human B cell immunity to the influenza hemagglutinin (HA) stem region, a universal influenza vaccine target, is often stereotyped and immunogenetically restricted, posing challenges for study outside humans. Here, we show that macaques vaccinated with a HA stem immunogen elicit human-like public B cell lineages targeting two major conserved sites of vulnerability, the central stem and anchor epitopes. Central stem antibodies were predominantly derived from VH1-138, the macaque homolog of human VH1-69, a VH-gene preferentially used in human central stem broadly neutralizing antibodies (bnAbs). Similarly, macaques produced anchor bnAbs with the human-like NWP motif. Both bnAb lineages were functionally and structurally analogous to their human counterparts, with recognition mediated largely by germline-encoded motifs. Thus the macaque immunoglobulin repertoire supports human-like public bnAb responses to influenza HA. Moreover, this underscores the utility of homologous germline-encoded immunity, suggesting that immune repertoires of macaques and humans may have been similarly shaped during evolution.Competing Interest StatementM.K. is named as an inventor on patents describing the HA stem immunogen used in this study under US10363301, US11147867, US11679151 which were filed by the Department of Health and Human Services.
ISSN:	2692-8205
DOI:	10.1101/2025.02.21.639368
Fuente:	Biological Science Database