tetano
Editor, Senior Moderator
Sci Transl Med
. 2025 Sep 10;17(815):eady3570.
doi: 10.1126/scitranslmed.ady3570. Epub 2025 Sep 10. Functional, immunogenetic, and structural convergence in influenza immunity between humans and macaques
Maya Sangesland[SUP] 1 [/SUP], Ning Li[SUP] 2 [/SUP], Yaroslav Tsybovsky[SUP] 2 [/SUP], Megan D Rodgers[SUP] 1 [/SUP], Julianna Han[SUP] 3 [/SUP], Alesandra J Rodriguez[SUP] 3 [/SUP], James A Ferguson[SUP] 3 [/SUP], Amy R Henry[SUP] 1 [/SUP], Sarah C Smith[SUP] 1 [/SUP], Jesmine Roberts-Torres[SUP] 1 [/SUP], Rebecca A Gillespie[SUP] 1 [/SUP], Cuiping Liu[SUP] 1 [/SUP], Jonah S Merriam[SUP] 1 [/SUP], Tyler Stephens[SUP] 2 [/SUP], Connor Williams[SUP] 4 [/SUP], Emma Walker[SUP] 4 [/SUP], Martin Corcoran[SUP] 5 [/SUP], Michelle Ravichandran[SUP] 1 [/SUP], Adrian Creanga[SUP] 1 [/SUP], Sarah F Andrews[SUP] 1 [/SUP], Theodore C Pierson[SUP] 1 [/SUP], Gunilla B Karlsson Hedestam[SUP] 5 [/SUP], Chaim A Schramm[SUP] 1 [/SUP], Douglas S Reed[SUP] 4 [/SUP], Daniel C Douek[SUP] 1 [/SUP], Tongqing Zhou[SUP] 1 [/SUP], Andrew B Ward[SUP] 3 [/SUP], Masaru Kanekiyo[SUP] 1 [/SUP]
Affiliations
Human B cell immunity to the influenza hemagglutinin (HA) stem, a universal vaccine target, is often stereotyped and immunogenetically restricted, posing hurdles to study outside of humans. Here, we show that cynomolgus macaques vaccinated with an HA stem immunogen elicit humanlike public B cell lineages targeting two major conserved sites of vulnerability, the central stem and anchor epitopes. Central stem antibodies were predominantly derived from V[SUB]H[/SUB]1-138, the macaque homolog of human V[SUB]H[/SUB]1-69, a V[SUB]H[/SUB] gene preferentially used in human central stem broadly neutralizing antibodies (bnAbs). Similarly, macaques produced anchor bnAbs containing the canonical NWP motif. Both bnAb lineages were functionally and structurally analogous to their human counterparts, with recognition mediated largely by germline-encoded structural motifs. These findings indicate that the macaque immunoglobulin repertoire can support humanlike public bnAb responses to influenza HA, highlighting the value of the macaque model for translational vaccinology. Moreover, this underscores the utility of homologous germline-encoded immunity, suggesting that immune repertoires of macaques and humans have been similarly shaped during evolution.
. 2025 Sep 10;17(815):eady3570.
doi: 10.1126/scitranslmed.ady3570. Epub 2025 Sep 10. Functional, immunogenetic, and structural convergence in influenza immunity between humans and macaques
Maya Sangesland[SUP] 1 [/SUP], Ning Li[SUP] 2 [/SUP], Yaroslav Tsybovsky[SUP] 2 [/SUP], Megan D Rodgers[SUP] 1 [/SUP], Julianna Han[SUP] 3 [/SUP], Alesandra J Rodriguez[SUP] 3 [/SUP], James A Ferguson[SUP] 3 [/SUP], Amy R Henry[SUP] 1 [/SUP], Sarah C Smith[SUP] 1 [/SUP], Jesmine Roberts-Torres[SUP] 1 [/SUP], Rebecca A Gillespie[SUP] 1 [/SUP], Cuiping Liu[SUP] 1 [/SUP], Jonah S Merriam[SUP] 1 [/SUP], Tyler Stephens[SUP] 2 [/SUP], Connor Williams[SUP] 4 [/SUP], Emma Walker[SUP] 4 [/SUP], Martin Corcoran[SUP] 5 [/SUP], Michelle Ravichandran[SUP] 1 [/SUP], Adrian Creanga[SUP] 1 [/SUP], Sarah F Andrews[SUP] 1 [/SUP], Theodore C Pierson[SUP] 1 [/SUP], Gunilla B Karlsson Hedestam[SUP] 5 [/SUP], Chaim A Schramm[SUP] 1 [/SUP], Douglas S Reed[SUP] 4 [/SUP], Daniel C Douek[SUP] 1 [/SUP], Tongqing Zhou[SUP] 1 [/SUP], Andrew B Ward[SUP] 3 [/SUP], Masaru Kanekiyo[SUP] 1 [/SUP]
Affiliations
- PMID: 40929243
- DOI: 10.1126/scitranslmed.ady3570
Human B cell immunity to the influenza hemagglutinin (HA) stem, a universal vaccine target, is often stereotyped and immunogenetically restricted, posing hurdles to study outside of humans. Here, we show that cynomolgus macaques vaccinated with an HA stem immunogen elicit humanlike public B cell lineages targeting two major conserved sites of vulnerability, the central stem and anchor epitopes. Central stem antibodies were predominantly derived from V[SUB]H[/SUB]1-138, the macaque homolog of human V[SUB]H[/SUB]1-69, a V[SUB]H[/SUB] gene preferentially used in human central stem broadly neutralizing antibodies (bnAbs). Similarly, macaques produced anchor bnAbs containing the canonical NWP motif. Both bnAb lineages were functionally and structurally analogous to their human counterparts, with recognition mediated largely by germline-encoded structural motifs. These findings indicate that the macaque immunoglobulin repertoire can support humanlike public bnAb responses to influenza HA, highlighting the value of the macaque model for translational vaccinology. Moreover, this underscores the utility of homologous germline-encoded immunity, suggesting that immune repertoires of macaques and humans have been similarly shaped during evolution.