The CM Study: Bivalent HIV Vaccine Induces Stronger T Cell Responses in People with HIV on ART

At CROI 2025, held March 9-12, in San Francisco, California, Nilu Goonetilleke, LLBHons, BScHons, PhD, associate professor at UNC School of Medicine, discussed The CM Study, a phase 1 trial investigating the ChAdOx1 and MVA-based HIVconsvX vaccine. The vaccine uses viral vectors to express the HIVconsvX immunogens, Mosaic-1 and Mosaic-2, and aims to induce HIV-specific T-cell responses in people with HIV (PWH) on ART. The study hypothesized that the bivalent regimen, including both immunogens, would elicit a stronger and broader T-cell response than the monovalent regimen. The findings showed that the bivalent vaccine induced a significantly greater T-cell response targeting both immunogens, supporting the hypothesis that a broader immune response could be achieved.

The study found that the monovalent (C62-M4) and bivalent (C1C62-M3M4) vaccine regimens were safe, with mild adverse events that resolved within 24 hours. The bivalent vaccine, which targets Mosaic-1 and Mosaic-2, induced higher T-cell responses, especially to Mosaic-1, at days 140 and 196, indicating a more sustained and broader immune response. The placebo group showed no significant changes in T-cell frequency.

This was a double-blind, randomized trial with participants on ART for at least 24 months and CD4 counts above 350 cells/mm³. The participants were divided into three groups:

• Group 1 received the monovalent vaccine (C62-M4)

-Day 0: 5x10^10 viral particles.

-Day 28: 1.8x10^8 plaque-forming units.

• Group 2 received the bivalent vaccine (C1C62-M3M4)

-Day 0: 2.5x10^10 viral particles.

-Day 28: 1.0x10^8 plaque-forming units.

• Group 3 received a placebo.

-Day 0 and Day 28: 0.9 mL of saline.

T-cell responses were measured using IFN-γ ELISpot assays, and virological endpoints, including low-level viremia and integrated DNA, were assessed. Linear regression was used to analyze the effect of ART duration on vaccine-induced T-cell responses.

Goonetilleke emphasized the safety profile of the vaccines, saying, “Both the MVA and ChAdOx1 vectors are attenuated viruses, meaning they cannot replicate. These viral vectors have been used safely in a variety of populations, including in smallpox vaccination and more recently in COVID-19 vaccines.”

Regarding the bivalent vaccine's effectiveness, Goonetilleke explained, “The bivalent regimen induced broader immune responses because it targets two different conserved regions of HIV. This could be crucial, as HIV is highly diverse and using multiple immunogens may help cover the variety of viral strains circulating within individuals.”

The study also revealed that participants in the bivalent group showed a stronger and more sustained immune response, particularly to Mosaic-1. Goonetilleke noted, “The bivalent vaccine produced responses to both Mosaic-1 and Mosaic-2, which suggests it could be more effective at targeting the diversity within the HIV reservoir.”

Looking ahead, Goonetilleke is optimistic about the implications for ART-free remission strategies. She added, “The fact that the bivalent vaccine induced a strong T-cell response in a small group of participants suggests that this approach could contribute to HIV cure strategies, especially in combination with other treatments.”

Future steps for this research include evaluating the vaccine’s effect on the HIV reservoir, with plans for post-hoc analyses to explore how age and ART duration impact T-cell responses. Goonetilleke concluded, “We are excited about further studies to refine these vaccines, especially in exploring how they can support ART-free remission for individuals living with HIV.”

Reference

Goonetilleke N, et al. ChAdOx1.HIVconsvX and MVA.HIVconsvX vaccination is safe and immunogenic in PWH on ART: The CM Study. Poster #428 presented at CROI 2025. March 9-12, 2025, San Francisco, California.