The M&M Study: Age-Related T Cell Response in People with HIV on ART in MVA.HIVconsvX Vaccine Trial

At CROI 2025, Nilu Goonetilleke, LLBHons, BScHons, PhD, associate professor at UNC School of Medicine, discussed The M&M Study, a Phase I trial investigating the MVA.HIVconsvX vaccine. The vaccine uses a Modified Vaccinia Ankara (MVA) vector to express HIVconsvX immunogens and aims to induce HIV-specific T-cell responses. The study examined the impact of age on immune responses to the vaccine in people with HIV (PWH) on ART, which suppresses but does not cure the infection. The results showed that while age was associated with a reduced T-cell response, the vaccine was safe and induced T-cell responses across all age groups.

The study found that vaccination increased HIV-specific T-cell responses in PWH on ART, with 11% of participants showing new responses. The magnitude of the T cell response decreased with age, showing a 50% reduction over a 20-year period. Longer ART duration was positively associated with stronger T-cell responses, suggesting ART may help mitigate age-related immune decline. Virological assessments showed no significant changes in low-level viremia or total integrated DNA, though a modest increase in intact integrated DNA was observed.

This was a double-blind, randomized trial. There were 21 participants on ART for at least 24 months with CD4 counts above 350 cells/mm³ were vaccinated with MVA-based vaccines expressing Mosaic-1 (M3), Mosaic-2 (M4), or both (M3+M4), or a placebo. T-cell responses were assessed using IFN-γ ELISpot assays, and virological endpoints, including low-level viremia and integrated DNA, were evaluated. Linear regression was used to analyze the impact of age and ART duration on vaccine-induced T-cell responses.

The MVA.HIVconsvX vaccine demonstrated a strong safety profile, with all adverse events being mild and resolving within 24 hours. Goonetilleke explained, “These are what we describe as viral-vectored vaccines, and the MVA used in this study is an attenuated virus that cannot replicate. It’s been tested in elderly individuals and newborns and has always been shown to be safe.”

The study revealed that older individuals had a lower T-cell response to the vaccine. Goonetilleke discussed this finding, “It is well documented that as we age, our immune response generally weakens. For T-cell vaccines like the MVA.HIVconsvX, our bodies become less capable of producing a broad and diverse range of T-cells, which is vital for the success of vaccination.”

Goonetilleke also pointed out that longer durations on ART were linked to better immune responses. She said, “What was particularly interesting about this study was that people who had been on ART for a longer period had better immune responses, which suggests that ART may help mitigate the effects of aging on immune function.”

Goonetilleke remains optimistic about the potential for future HIV vaccines. She highlighted that the MVA.HIVconsvX vaccine induced a robust immune response in nearly 85% of participants, regardless of their age, which suggests strong potential for widespread vaccine applicability. “This is a vaccine designed to target the conserved regions of HIV, which is promising because it can work across a diverse population of PWH,” she said.

Looking ahead, Goonetilleke noted that strategies such as booster doses or modified vaccination regimens could enhance the immune response, particularly for older individuals. “For people who are older, we’re looking at doing boosting vaccinations or modifying the vaccine to better focus the immune response against HIV.”

Reference

Goonetilleke N, et al. Age inversely correlates with T-cell response to MVA.HIVconsvX vaccination in PWH on ART. Poster #425 presented at CROI 2025. March 9-12, 2025, San Francisco, California.