Co-evolution of antibody responses against human immunodeficiency virus (HIV-1) envelope

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Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B143
Abstract ID: 4432

Presenting Author:
Juhi Arora , Postdoctoral Fellow at Henry M. Jackson Fndn. for the Advancement of Mil. Med., Walter Reed Army Institute of Research (WRAIR), U.S. Military HIV Research Program (MHRP)

Abstract:

Broadly neutralizing antibodies (bNAbs) target epitopes on the Envelope (Env) glycoprotein of HIV-1 and neutralize diverse strains with high breadth and potency. Studying the ontogeny of bNAb development will help identify better immunogens for vaccine design. RV217 is an acute infection cohort with samples collected prior to seroconversion and continued 2+ years following detection of viral RNA (RNA+). From participant 40512, living with CRF01_AE infection, we isolated several bNAbs at day 646 post-RNA+ that targeted the membrane proximal external region (MPER) on the HIV Env. These included the VRC42 lineage, with neutralization breadth of 97% on multi-subtype pseudovirus panels. Sequence analysis revealed sequential mutations in the HIV-1 Env, indicating virus evolution. The participant acquired another CRF01_AE HIV-1 infection (i.e., superinfection) between days 330-401 post-RNA+, increasing antigenic diversity, and continued to develop breadth to 98% at day 1142 post-RNA+. Using rapid amplification, transfection, and production of immunoglobulins (RATP-Ig), we sorted MPER+ B cells and isolated an additional 22 VRC42 lineage mAbs at day 1142 post-RNA+. Interestingly, origins of the 4 sublineages were traced back to day 154 post-RNA+. These mAbs continued to evolve out to day 1142 and showed greater activity against late autologous viruses, suggesting that co-evolving HIV-1 Env and antibodies led to development of neutralization breadth.