Fusion peptide-directed HIV-1-neutralizing antibodies from vaccinated guinea pigs

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Presentation Time: 03:15 PM - 04:30 PM
Poster Board Number: B966
Abstract ID: 7704

Presenting Author:
Katelyn T Nguyen , Postbaccalaureate Researcher at NIAID, NIH

Abstract:

Eliciting broad and potent neutralizing antibodies (bnAbs) to generate protective immunity remains a key goal of HIV-1 vaccine research. One promising epitope for bnAb targeting is the HIV-1 fusion peptide (FP), a functionally critical region on the HIV-1 envelope trimer. Guinea pigs (GPs) as model organisms are deeply informative, and cross-clade neutralizing FP-directed responses have been elicited in GPs by vaccination; however, cloning antibodies from GPs is challenging because well-characterized reagents and antibody germline sequences are limited. Here, we investigate characteristics of GP antibodies elicited by FP prime, HIV-1 trimer boost regimens that induced weak FP-directed neutralization in serum to multiple heterologous viral strains. From 20 FP-vaccinated GPs, we isolated FP and HIV-1 trimer double-positive B cells from PBMCs and terminal splenocytes by cell sorting, followed by 10x genomic sequencing to identify antibody sequences. These sequences were used for gene synthesis and IgG production, which were further screened for binding and neutralization. Several IgGs bound BG505, ConC, and FP, and neutralized the homologous clade A BG505 strain used in immunization, and at least one IgG also neutralized the heterologous clade C strain 25710. We are isolating and characterizing antibodies, including by cryo-EM analysis, to identify more monoclonals that recapitulate the cross-clade FP-directed neutralization observed in GP-vaccinated serum.