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Publications of the Week

Analysis of the HVTN 702 Phase 2b-3 HIV-1 Vaccine Trial in South Africa Assessing RV144 Antibody and T Cell Correlates of HIV-1 Acquisition Risk

By July 14, 2022No Comments

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This week we profile a recent publication in The Journal of Infectious Diseases from Dr. Zoe Moodie (left) and the laboratory of Dr. Juliana McElrath (right) at Fred Hutch.

Can you provide a brief overview of your lab’s current research focus?

The McElrath laboratory applies multi-disciplinary and cross-platform approaches to their studies, which encompass the following research areas: HIV Vaccine Trials Network (HVTN) Laboratory, Cape Town HVTN, Immunology Laboratory, Seattle Vaccine Trials Unit, Coronavirus, Malaria & Tuberculosis Vaccines
Infectious Diseases Clinical Research Consortium, Long Term Non-Progressor Cohort.

What is the significance of the findings in this publication?

Since the establishment of immune correlates of HIV-1 acquisition risk in the RV144 efficacy trial of an ALVAC/gp120 pox-protein HIV-1 vaccine regimen in a Thai population, it has remained an open question whether these correlates are generalizable to other populations. We report that the immune response profile induced in HVTN 702 showed some differences from that induced in RV144 and that polyfunctional CD4+ Env-ZM96 responses correlated with HIV-1 risk given qualitative IgG A244 V2V2 bAb response level. This raises the hypothesis that ALVAC/gp120 vaccination needs to induce high bAb V1V2 responses, in combination with polyfunctional CD4 T cell responses, to achieve protection from HIV. These findings are important for helping gather the maximum scientific knowledge from the valuable data collected in this large HIV-1 vaccine efficacy trial and for steering further HIV-1 vaccine development.  

What are the next steps for this research?

The next steps are to conduct a sieve analysis of the HIV viral sequences to examine whether the HVTN 702 vaccine regimen exerted immune pressure on breakthrough viruses​.

If you’d like us to mention your funding sources, please list them.

This study was supported by the National Institutes of Health, National Institute of Allergy and Infectious Diseases (NIAID) (UM1 AI068614, to the HIV Vaccine Trials Network [HVTN]; UM1 AI068635, to the HVTN Statistical Data and Management Center [SDMC], Fred Hutchinson Cancer Research Center [FHCRC]; UM1 AI068618, to HVTN Laboratory Center, FHCRC; with additional support by the Center for AIDS Research, Duke University (AI P30 AI064518). Funding was provided to Novartis Vaccines and Diagnostics (now part of the GlaxoSmithKline Biologicals SA) by NIAID (HHSN272201300033C//HHSN272201600012C) for the selection and process development of the two gp120 envelope proteins TV1.C and 1086.C, and by the Bill & Melinda Gates Foundation Global Health Grant OPP1017604 and NIAID for the manufacture and release of the gp120 clinical grade material.

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