Investigating Broad Neutralization in HIV-1 Non-B Subtype Infection in Yaoundé, Cameroon

Abstract

P16.03 Background: A hallmark of HIV is its variability, which within group M viruses includes 9 subtypes and over 50 circulating recombinant forms (CRF)s. Cameroon is an epicenter of the disease known for circulation of many subtypes and CRFs, which provides a unique setting to study the immune response to HIV. It is crucial for a successful vaccine to elicit an adaptive immune response against a broad range of viral subtypes. Methods: We have performed subtype analysis of viral RNA isolated from the plasma of 63 HIV-1 infected Cameroonian subjects to verify non-B subtype infection and to monitor for recombination. From the non-B, drug naive cohort, we have isolated IgG (N=264) to screen for neutralization using a tier 2, pseudovirus panel including subtypes A1, B, C, and 01_AE. Samples capable of neutralizing multiple pseudoviruses at high potency were selected for further study to determine neutralization capacity against an extended panel and their ability to bind gp160 envelope peptides. Results: Subtypes A, D, F, G, and K were identified as well as many recombinant forms including the predominant subtype CRF02_AG. The neutralization screen concluded that 9.5% of the IgG samples were able to neutralize at least 2 pseudoviruses at low IgG concentrations. Neutralization of the extended panel revealed that these IgG samples were also able to neutralize 02_AG,G, and AC subtypes. We found that all of the broadly neutralizing IgG samples bound envelope protein gp41, over 80% bound gp120 proteins, 79% bound a scaffolded V1V2 peptide, and 100% of the samples bound cyclic V3 constructs. Conclusions: We have taken the first look at broad neutralization in a cohort infected with non-B subtype viruses and numerous CRFs. IgG from these patients is capable of neutralizing pseudoviruses across clades with high breadth and potency. We have shown that these samples bind strongly to envelope peptides and hope to continue to elucidate how these antibodies are conferring neutralization in order to guide future vaccine design.