In a statement from the University of Oxford in July 2023 it was announced that preliminary analysis of vaccine trial results demonstrates the induction of “high frequencies” of broadly specific T cells. These cells recognise “functionally conserved regions on HIV-1 and are consequently “more protective”. The statement indicates that “not all T cells are equally protective”, with the T cells induced by the vaccine candidate, often “underutilised in natural HIV-1 infection. These T cells, known as killer T cells, could inhibit four major global HIV clades: A, B, C, and D. Further analyses continue, with first results expected in a publication later in the year.
The goal of the trial is to evaluate the safety, tolerability, and immunogenicity of the novel mosaic HIV vaccine candidate, HIVconsvX. It has been designed to target a broad range of variants, which could allow application for strains in any geographical region. Unlike many other candidates, which aim to generate antibody or T cell responses against more variable HIV epitopes, HIVconsvX aims to “induce the immune system’s killer T cells against a group of highly conserved regions”. These “obliterate the virus factories in the body”.
HIV-CORE 006 is a Phase I double-blind, placebo-controlled trial. Mosaic immunogens are delivered by a prime-boost regimen of non-replicating simian adenovirus, followed by non-replicating poxvirus MVA. Volunteers, comprising up to 88 healthy African adults between the ages of 18 and 50, who are HIV-uninfected and deemed at low risk of infection, were either given the vaccine regimen or placebo at 2 visits 4 weeks apart. The trial took place across four vaccine trial sites in Kenya, Uganda, and Zambia.
The trial is the work of the GREAT team from 8 organisations in Europe and Africa, led by Professor Tomáš Hanke of the Jenner Institute. The team comes from Imperial College London, IAVI, KAVI-Institute for Clinical Research, KEMRI-Wellcome Trust Research Programme, the Medical Research Council at the Uganda Virus Research Institute on AIDS, the UVRI-IAVI HIV Vaccine Programme in Uganda, and the Centre for Family Health Research in Zambia. The programme is supported by the European & Developing Countries Clinical Trials Partnership.
Professor Hanke commented that the study team has evaluated a “highly rational, bioinformatics-assisted vaccine design to address the enormous variability of HIV-1″. This is one of the “greatest challenges to the development of an effective vaccine against HIV/AIDS”, he says.
“The analysis so far indicates the induction of strong and multi-specific T cell responses that recognise several vulnerable parts of proteins common to most HIV variants in each individual at the same time – targeting HIV where it hurts.”
Dr William Kilembe, Project Director at the Centre for Family Health Research in Zambia, recognised that the GREAT consortium “leveraged international partnerships” in Africa and Europe to test the vaccine in the communities where it would “ultimately have the greatest public health impact”.
“Through this trial, the consortium members have contributed to strengthening the capacity of the partnering clinical research centres to conduct robust HIV vaccine research and clinical trials.”
“Community engagement is key to this approach, and we look forward to continuing to work with community stakeholders as the final results become available.”
An important step
Dr Vincent Muturi-Kioi, Senior Medical Director at IAVI, said that the study represents an “innovative hypothesis” to “harness the killer T cell arm of the immune system”.
“It’s important that we have a diversity of vaccine candidates in the pipeline to make sure we have the greatest chance of success in developing an effective HIV vaccine.”
Dr Paola Cicconi, Senior Clinical Researcher at the Jenner Institute, was pleased that the vaccines used in trial “demonstrated a favourable safety profile” as well as the induction of an immune response in “most of the participants”.
“These are promising results, and an important step in developing an HIV vaccine that can protect people against HIV infection in all parts of the world.”
The next stage will be the release of primary findings later in the year and additional analyses.
Do you think the approach could lead to a greater step forward than previous vaccine candidates? To hear a little more about the challenges associated with HIV vaccine development, check out our interview with Dr Gaurav Gaiha from the Congress in Washington earlier this year.
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