Primed B cells continue to undergo affinity maturation in people living with HIV-1 when ART is provided in acute infection 4109

Abstract Description Protective, high affinity antibodies develop via mutagenesis and an iterative selection process in germinal centers called affinity maturation. For highly variable pathogens such as HIV-1, understanding the kinetics of antibody affinity maturation against viral envelope glycoproteins (Envs) in people with HIV (PWH) with or without anti-retroviral therapy (ART) will be beneficial in identifying immunogens that stimulate desirable antibody production. Here, plasma binding affinity against subtype CRF01_AE founder Envs was measured using biolayer interferometry for RV254 Thai participants treated within acute stages of infection (Fiebig I-VI) and untreated RV217 Thai and African participants who were captured prior to seroconversion through 2+ years post viral RNA detection (pRNA+). After ART initiation during acute infection, affinity (measured by the dissociation constant, Kdis) significantly increased after 24 weeks of ART, indicating ongoing affinity maturation in the waning presence of viral load (p < 0.001). Affinity to HIV Env in ART-initiated RV254 participants was comparable to the ART-naïve RV217 participants during chronic stages of infection (Kdis = 3.6e-4 to 1.7e-3/sec). These data indicate that primed B cells can undergo antibody affinity maturation regardless of early ART initiation and provide potential targets for future therapeutic vaccine designs. Topic Categories Viral Immunology (VIR)