MVA.HIVconsvX vaccination-evoked T cell expansion inversely associates with age in people with HIV-1 on antiretroviral therapy.

BACKGROUNDApproaches to achieving antiretroviral therapy-free (ART-free) remission from HIV-1 must consider that people over 50 years now comprise the majority of people with HIV (PWH) on ART in various regions, including the United States.METHODSWe report a double-blind, randomized trial in which PWH on ART, aged 21-60 years, received modified vaccinia Ankara-vectored (MVA-vectored) vaccines, MVA.tHIVconsv3 (M3) and MVA.tHIVconsv4 (M4), either alone or in combination (n = 7/group), or saline placebo (n = 3). M3 and M4 contain complementary HIVconsvX immunogens that each span the same regions in HIV-1 Gag and Pol but differ by approximately 8% at the amino acid level.RESULTSM3, M4, and M3M4 regimens were well tolerated and all significantly increased both the frequency (peak median increase ~3-fold) and breadth of the HIVconsvX-specific T cell response while redirecting T cells to target conserved regions in HIV-1 for up to 10 weeks after vaccination. We also demonstrated that vaccination increased frequencies of T cells targeting participant autologous HIV-1 sequences. Vaccination mostly expanded preexisting HIV-1-specific T cells and did not impact CD4+ T cell activation, low-level viremia, or integrated HIV-1 provirus. Linear regression indicated that age was independently and negatively associated with the change in T cell frequency at 1, 2, and 10 weeks after vaccination (~1.41-fold decrease per 10 years older). After adjusting for age, years on ART was positively associated with HIVconsvX-specific T cell frequencies at 1 and 2 weeks following vaccination.CONCLUSIONIn PWH receiving ART, MVA.HIVconsvX vaccines significantly increased T cells targeting conserved regions of HIV-1. Novel strategies may be required to enhance anti-HIV-1 immunity in older adults.TRIAL REGISTRATIONClinicalTrials.gov NCT03844386FUNDINGNIH National Institute of Allergy and Infectious Diseases (NIAID) grants U01AI131310, HHSN272201100021I/HHSN27200037 (subcontract OX-14007.004.0037-212), UM1TR004406, P30AI050410, and P30CA016086; International AIDS Vaccine Initiative; European and Developing Countries Clinical Trials Partnership SRIA2015-1066; European Commission's Horizon 2020 Research and Innovation Programme 681137.