| First Author | Sangesland M | Year | 2019 |
| Journal | Immunity | Volume | 51 |
| Issue | 4 | Pages | 735-749.e8 |
| PubMed ID | 31563464 | Mgi Jnum | J:282647 |
| Mgi Id | MGI:6381282 | Doi | 10.1016/j.immuni.2019.09.001 |
| Citation | Sangesland M, et al. (2019) Germline-Encoded Affinity for Cognate Antigen Enables Vaccine Amplification of a Human Broadly Neutralizing Response against Influenza Virus. Immunity 51(4):735-749.e8 |
| abstractText | Antibody paratopes are formed by hypervariable complementarity-determining regions (CDRH3s) and variable gene-encoded CDRs. The latter show biased usage in human broadly neutralizing antibodies (bnAbs) against both HIV and influenza virus, suggesting the existence of gene-endowed targeting solutions that may be amenable to pathway amplification. To test this, we generated transgenic mice with human CDRH3 diversity but simultaneously constrained to individual user-defined human immunoglobulin variable heavy-chain (VH) genes, including IGHV1-69, which shows biased usage in human bnAbs targeting the hemagglutinin stalk of group 1 influenza A viruses. Sequential immunization with a stalk-only hemagglutinin nanoparticle elicited group 1 bnAbs, but only in IGHV1-69 mice. This VH-endowed response required minimal affinity maturation, was elicited alongside pre-existing influenza immunity, and when IGHV1-69 B cells were diluted to match the frequency measured in humans. These results indicate that the human repertoire could, in principle, support germline-encoded bnAb elicitation using a single recombinant hemagglutinin immunogen. |
