tetano
Editor, Senior Moderator
Immunity
. 2024 Apr 18:S1074-7613(24)00143-2.
doi: 10.1016/j.immuni.2024.03.022. Online ahead of print. Eliciting a single amino acid change by vaccination generates antibody protection against group 1 and group 2 influenza A viruses
Rashmi Ray[SUP] 1 [/SUP], Faez Amokrane Nait Mohamed[SUP] 2 [/SUP], Daniel P Maurer[SUP] 1 [/SUP], Jiachen Huang[SUP] 3 [/SUP], Berk A Alpay[SUP] 4 [/SUP], Larance Ronsard[SUP] 1 [/SUP], Zhenfei Xie[SUP] 1 [/SUP], Julianna Han[SUP] 3 [/SUP], Monica Fernandez-Quintero[SUP] 5 [/SUP], Quynh Anh Phan[SUP] 1 [/SUP], Rebecca L Ursin[SUP] 1 [/SUP], Mya Vu[SUP] 1 [/SUP], Kathrin H Kirsch[SUP] 1 [/SUP], Thavaleak Prum[SUP] 1 [/SUP], Victoria C Rosado[SUP] 1 [/SUP], Thalia Bracamonte-Moreno[SUP] 1 [/SUP], Vintus Okonkwo[SUP] 1 [/SUP], Julia Bals[SUP] 1 [/SUP], Caitlin McCarthy[SUP] 1 [/SUP], Usha Nair[SUP] 1 [/SUP], Masaru Kanekiyo[SUP] 6 [/SUP], Andrew B Ward[SUP] 3 [/SUP], Aaron G Schmidt[SUP] 7 [/SUP], Facundo D Batista[SUP] 8 [/SUP], Daniel Lingwood[SUP] 9 [/SUP]
Affiliations
Broadly neutralizing antibodies (bnAbs) targeting the hemagglutinin (HA) stem of influenza A viruses (IAVs) tend to be effective against either group 1 or group 2 viral diversity. In rarer cases, intergroup protective bnAbs can be generated by human antibody paratopes that accommodate the conserved glycan differences between the group 1 and group 2 stems. We applied germline-engaging nanoparticle immunogens to elicit a class of cross-group bnAbs from physiological precursor frequency within a humanized mouse model. Cross-group protection depended on the presence of the human bnAb precursors within the B cell repertoire, and the vaccine-expanded antibodies enriched for an N55T substitution in the CDRH2 loop, a hallmark of the bnAb class. Structurally, this single mutation introduced a flexible fulcrum to accommodate glycosylation differences and could alone enable cross-group protection. Thus, broad IAV immunity can be expanded from the germline repertoire via minimal antigenic input and an exceptionally simple antibody development pathway.
Keywords: human antibody repertoire; immunogen; influenza virus; somatic hypermutation; universal; vaccine.
. 2024 Apr 18:S1074-7613(24)00143-2.
doi: 10.1016/j.immuni.2024.03.022. Online ahead of print. Eliciting a single amino acid change by vaccination generates antibody protection against group 1 and group 2 influenza A viruses
Rashmi Ray[SUP] 1 [/SUP], Faez Amokrane Nait Mohamed[SUP] 2 [/SUP], Daniel P Maurer[SUP] 1 [/SUP], Jiachen Huang[SUP] 3 [/SUP], Berk A Alpay[SUP] 4 [/SUP], Larance Ronsard[SUP] 1 [/SUP], Zhenfei Xie[SUP] 1 [/SUP], Julianna Han[SUP] 3 [/SUP], Monica Fernandez-Quintero[SUP] 5 [/SUP], Quynh Anh Phan[SUP] 1 [/SUP], Rebecca L Ursin[SUP] 1 [/SUP], Mya Vu[SUP] 1 [/SUP], Kathrin H Kirsch[SUP] 1 [/SUP], Thavaleak Prum[SUP] 1 [/SUP], Victoria C Rosado[SUP] 1 [/SUP], Thalia Bracamonte-Moreno[SUP] 1 [/SUP], Vintus Okonkwo[SUP] 1 [/SUP], Julia Bals[SUP] 1 [/SUP], Caitlin McCarthy[SUP] 1 [/SUP], Usha Nair[SUP] 1 [/SUP], Masaru Kanekiyo[SUP] 6 [/SUP], Andrew B Ward[SUP] 3 [/SUP], Aaron G Schmidt[SUP] 7 [/SUP], Facundo D Batista[SUP] 8 [/SUP], Daniel Lingwood[SUP] 9 [/SUP]
Affiliations
- PMID: 38670113
- DOI: 10.1016/j.immuni.2024.03.022
Broadly neutralizing antibodies (bnAbs) targeting the hemagglutinin (HA) stem of influenza A viruses (IAVs) tend to be effective against either group 1 or group 2 viral diversity. In rarer cases, intergroup protective bnAbs can be generated by human antibody paratopes that accommodate the conserved glycan differences between the group 1 and group 2 stems. We applied germline-engaging nanoparticle immunogens to elicit a class of cross-group bnAbs from physiological precursor frequency within a humanized mouse model. Cross-group protection depended on the presence of the human bnAb precursors within the B cell repertoire, and the vaccine-expanded antibodies enriched for an N55T substitution in the CDRH2 loop, a hallmark of the bnAb class. Structurally, this single mutation introduced a flexible fulcrum to accommodate glycosylation differences and could alone enable cross-group protection. Thus, broad IAV immunity can be expanded from the germline repertoire via minimal antigenic input and an exceptionally simple antibody development pathway.
Keywords: human antibody repertoire; immunogen; influenza virus; somatic hypermutation; universal; vaccine.