Germline-targeting vaccination elicits HIV broadly neutralizing antibodies in nonhuman primates

Описание: 2026 Immcantation Users Group Meeting https://immcantation.github.io/users-...
Title: Germline-targeting vaccination elicits HIV broadly neutralizing antibodies in nonhuman primates
Speaker: Patrick Madden, La Jolla Institute for Immunology (US)
Abstract:
Germline-targeting and shepherding is an HIV vaccine strategy that relies on multiple phases, priming of rare precursor B cells followed by maturation of those B cells into broadly-neutralizing antibodies (bnAbs) through sequential immunizations and, finally, conversion of those bnAb-expressing B cells into long-lived responses. We recently demonstrated that the priming immunogen N332-GT5 can reproducible prime BG18 type I precursor B cells in rhesus macaques. BG18 is an HIV bnAb that targets the N332 glycan supersite on the Envelope protein and is dependent on a long CDRH3 which makes the precursors incredibly rare in the naïve repertoire (1 in 53 million in humans and estimated 8-fold lower in NHPs). To extend these findings we initiated a study using sequential immunization of progressively more native like trimer immunogens after N332-GT5 ED priming to mature the BG18 type I responses. After a series of seven booster immunizations, over 50% of immunized animals developed BG18 type I like bnAb responses and demonstrated broad-neutralization in the serum. Through the use of the Immcantation framework, individual BG18 type I B cell lineages were traced throughout the study. Dowser was used to construct phylogenetic trees and trace the mutation history and development of neutralization potency and breadth in individual clonal families of up to 6000 cells, highlighting the importance of robust bioinformatic packages such as Dowser to aid in the analysis of germline-targeting vaccine regimens. Overall, these results show that germline-targeting can successfully induce bnAbs and serves as proof-of-concept that germline-targeting is a feasible vaccination strategy against HIV.