CROI 2017 Abstract e-Book

Abstract eBook

Poster and Themed Discussion Abstracts

244 INITIAL HIV DIVERSITY & NEUTRALIZING ANTIBODY DEVELOPMENT IN PEOPLE WHO INJECT DRUGS Andrew D. Redd 1 , Nicole Doria-Rose 2 , Matthew Seivers 3 , Stephen Schmidt 1 , Oliver Laeyendecker 1 , Stephen Porcella 4 , Gregory D. Kirk 3 , John R. Mascola 5 , Shruti H. Mehta 3 , Thomas C. Quinn 1 1 NIAID, Bethesda, MD, USA, 2 NIH, Bethesda, MD, USA, 3 The Johns Hopkins Univ, Baltimore, MD, USA, 4 NIAID, Hamilton, MT, USA, 5 Vaccine Rsr Cntr, Bethesda, MD, USA Background: Any successful protective HIV vaccine will most likely need to generate a broad and diverse antibody response that can directly neutralize (NAb), or bind and direct virions to other cytotoxic mechanisms. An important underlying element of any vaccine construct is the ability to generate a similar immune response in a majority of vaccinees. Yet, currently it is unknown if in natural HIV infection, individuals initially infected with similar viral strains generate analogous humoral immune responses. This project examined whether initial viral genetic diversity between individuals predicted maturation pattern, strength, and breadth of the anti-HIV NAb response 3-6 years post-infection. Methods: Recently infected HIV+ persons who inject drugs (PWID) were identified using a multi-assay algorithm from individuals who entered the AIDS Linked to the Intravenous Experience (ALIVE) study prevalently positive at enrollment (1988-89; n=23). The enrollment sample from these individuals was examined using next-generation sequencing (NGS) to examine HIV genetic diversity (HIV-SI) in two genetic regions (gp41 and pol). Viral sequences were combined to make a universal consensus sequence which was concatenated, and examined in a maximum likelihood phylogenetic tree. The NAb response in these individuals 3-6 years post-HIV diagnosis was determined using a standard panel of 21 heterologous viral isolates with multiple subtypes (A, B, and C). The NAb patterns from these individuals were analyzed for NAb fingerprint signatures that indicate the targeted epitopes. Results: Three groups of individuals were identified who were initially infected in 1988-89 with highly similar viruses (<2% genetic distance; n=5, 5, & 6 respectively), as well as a group of non-clustered individuals (n=6; Figure 1). It was observed that the neutralization fingerprint for cluster one was significantly more correlated than the other samples (permutation test, p=0.043), and that cluster three had significantly stronger response to three viruses in the neutralization panel (p<0.05). Conclusion: These data suggest that limited initial viral diversity between individuals can lead to similar NAb responses years later. It will be important to determine when and how these anti-HIV responses develop in these subjects, and if this phenomenon is seen in other risk groups. Although these data are preliminary, these findings are encouraging news for the prospects of developing universal vaccine strategies against HIV.

Poster and Themed Discussion Abstracts

245 ELITE NEUTRALIZATION AND UNIQUE EPITOPE SPECIFICITY OF A VIREMIC NONPROGRESSOR Nandagopal Paneerselvam 1 , Chinnambedu Ravichandran Swathirajan 1 , Sunil S. Solomon 1 , Jayantha Bhattacharya 2 , Bimal K. Chakrabarti 2 , Rajat Goyal 3 , Aylur K. Srikrishnan 1 , Kailapuri G. Murugavel 1 1 YRG CARE, Chennai, India, 2 HIV Vaccine Translational Rsr Lab, Faridabad, India, 3 Intl AIDS Vaccine Initiative, New York, NY, USA Background: In HIV infection, only 10-30% of the individuals are able to generate broadly neutralizing antibody response (bnAbs).Development of bnAb response was significantly associated with duration of infection, high viral load and low CD4 counts among typical progressors. Conversely, HIV-1 viremic non-progressors are individuals who maintain higher CD4 counts with moderate viral load without asymptomatic for > 7 yrs of infection. However, bnAb response has not been described among HIV-1 viremic non- progressors Methods: In this study, plasma samples from a cohort of 90 ART-Naive HIV-1 infected individuals with various disease progression stages were tested against Tier-2 global virus panel (n=11) includes subtype A, B C, G, AC, BC & AE. The cohort includes viremic controllers, viremic non-progressors and typical progressors. The epitope mapping by ELISAs, neutralization of V2 (N160A &R166A) &V3 (N301A &N332A) point mutants and protein competition neutralization assay with MPER &RSC3 antigens. Samples that are able to neutralize >50% of virus with ID[50] >100 (moderate neutralization), were then tested against an extended virus panel (n=19) to find Elite neutralization. Elite neutralizers are those able to neutralize >75% of viruses tested with ID[50] >100 and geometric mean ID[50] > 500.

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CROI 2017