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TitleFunctional, Immunogenetic, and Structural Convergence in Influenza Immunity between Humans and Macaques.
Journal, issue, pagesbioRxiv, Year 2025
Publish dateFeb 27, 2025
AuthorsMaya Sangesland / Ning Li / Yaroslav Tsybovsky / Megan D Rodgers / Julianna Han / Alesandra J Rodriguez / James A Ferguson / Amy R Henry / Sarah C Smith / Jesmine Roberts-Torres / Rebecca A Gillespie / Cuiping Liu / Jonah S Merriam / Tyler Stephens / Connor Williams / Emma Maestle / Martin Corcoran / Michelle Ravichandran / Adrian Creanga / Sarah F Andrews / Theodore C Pierson / Gunilla B Karlsson Hedestam / Chaim A Schramm / Douglas S Reed / Daniel C Douek / Tongqing Zhou / Andrew B Ward / Masaru Kanekiyo /
PubMed AbstractHuman 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 ...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 V1-138, the macaque homolog of human V1-69, a V-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.
External linksbioRxiv / PubMed:40568173 / PubMed Central
MethodsEM (single particle)
Resolution3.7 - 20.0 Å
Structure data

45636

9cjy

EMDB-45636, PDB-9cjy:
CryoEM structure of NC99 hemagglutinin trimer in complex with Fab BB798E 3-C07
Method: EM (single particle) / Resolution: 3.7 Å

45637

9cjz

EMDB-45637, PDB-9cjz:
CryoEM structure of NC99 hemagglutinin trimer in complex with Fab T009 3-E04
Method: EM (single particle) / Resolution: 3.8 Å

EMDB-46824: Polyclonal immune complex of human subject 321-2006 Fab binding H1 HA
Method: EM (single particle) / Resolution: 20.0 Å

EMDB-46825: Polyclonal immune complex of human subject 321-2009 Fab binding H1 HA
Method: EM (single particle) / Resolution: 20.0 Å

EMDB-46827: Polyclonal immune complex of human subject 321-2012 Fab binding H1 HA
Method: EM (single particle) / Resolution: 20.0 Å

EMDB-46829: Polyclonal immune complex of Fab from Cynomolgus Macaque 6974 at week 12 binding H1 HA
Method: EM (single particle) / Resolution: 20.0 Å

EMDB-46830: Polyclonal immune complex of Fab from Rhesus Macaque BB798E at week 12 binding H1 HA
Method: EM (single particle) / Resolution: 20.0 Å

EMDB-46831: Polyclonal immune complex of Fab from Cynomolgus Macaque T009 at week 12 binding H1 HA
Method: EM (single particle) / Resolution: 20.0 Å

EMDB-46832: Polyclonal immune complex of Fab from Cynomolgus Macaque R996 at week 12 binding H1 HA
Method: EM (single particle) / Resolution: 20.0 Å

Source
  • influenza a virus
  • macaca fascicularis (crab-eating macaque)
  • Homo sapiens (human)
KeywordsVIRAL PROTEIN / Immune system / Hemagglutinin / Fab / Macaque

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