HIVconsvX Vaccine Shows Safety, Immune Response in People on ART

Modified vaccinia Ankara–vectored vaccines using the Mosaic-1 and Mosaic-2 immunogens (collectively HIVconsvX) to target the same 6 HIV regions are safe to use and elicited an immune response in people living with HIV and currently taking antiretroviral therapy (ART), according to new findings from the M&M study presented at the 2025 Conference on Retroviruses and Opportunistic Infections by Nilu Goonetilleke, PhD, associate professor of medicine at the University of North Carolina School of Medicine.

This research on a T-cell–targeting vaccines in HIV has implications for future study design to incorporate consideration of age and years on ART to evaluate the level of immune reconstitution.

This transcript has been lightly edited for clarity; captions were auto-generated.

Transcript

Does age impact the immune response to the MVA.HIVconsvX vaccine in people with HIV on ART, and could HIV infection further exacerbate this effect?

The first thing I would say is we have not seen, and I haven't seen it reported, that what we describe as our baseline, a prevaccination response to HIV, that the magnitude or the amount of T cells targeting HIV are different based on age. We don't see an age relationship. What we observed in this trial was very much what we describe as a linear relationship between age and your immune response. What was very notable, that I haven't seen reported before, is this linear relationship. Our study had participants from 20 to 60—they weren't all older—and so we saw that even from 20 to 30 to 40 to 50 to 60, you had this sort of loss in your ability to increase response.

The question is, is that linear relationship more acute, more exacerbated by somebody’s previous HIV infection? We don't know that, so we have to work that one out particularly. Where it's really relevant in the US for care is, over 50% of people living with HIV in the US are over 50, and that number is just growing. This isn't a special group of older individuals. This is our community in the US, and so we actually have to now go in with not special regimens, the regimens now have to account for age.

How can booster strategies and vaccine design improve HIV-specific T-cell responses in older adults on ART?

It’s the idea of boosters. It's the idea of perhaps…we give them different types of vaccines that might hit different parts of the immune response but contain the same bits of HIV. We're really trying to each time focus the immune response on HIV and boost and boost and boost. The next study we'd really like to do is with a network called the ACTG [AIDS Clinical Trials Group], which you may have heard of. I'd really like to do a study in a very controlled way where participants, we ensure they're across a broad age range, from 20 to as high as it can get. But also, the flip side, they have different ranges of years on ART. The longer you are on ART, the better your immune response.

If we almost have sort of a checkerboard or a matrix, and then we vaccinate, and we look at their immune response after the first vaccination, I'd like to then do a second vaccination, where half of the participants are vaccinated and half aren't and to see if really, hammer down, does that improve it? I think once we do a study like that that's really well controlled, my goal is, well, okay, then we're really going to be able to model what we do for the biggest studies as we move forward. So that's, that's hopefully our short-term plan.