Background
Durable antiviral therapy (ART)-free remission from HIV-1 will likely require a robust and targeted T-cell response to limit viral reactivation. Serial vaccination with different viral vectors expressing the same immunogen has induced higher T-cell frequencies than homologous vaccination regimens.
Methods
The CM study is a double-blind, randomized, phase I vaccine trial which recruited people with HIV (PWH) suppressed on ART for >24 months. The study vaccines were ChAdOx1.tHIVconsv1 (C1) and ChAdOx1.HIVconsv62 (C62) followed by MVA.tHIVconsv3 (M3) and MVA.tHIVconsv4 (M4) at 28 days, all given intramuscularly. Vaccines expressed conserved Gag and Pol regions as mosaic 1 (C1 and M3) and mosaic 2 (C62 and M4), which differed in ~8% of amino acids. Participants were randomized to regimens C62-M4 (mosaic 1), C1C62-M3M4 (mosaics 1 and 2) or placebo (Table 1). Exclusion criteria included history of clotting disorders and prior vaccination with MVA-mpox and ChAdOx1 nCoV-19 vaccines. Immunogenicity endpoints were measured using IFN-γ ELISpot.
Results
Enrollment is complete with 18 participants 24-67 years of age, 16.7% female, 44% black/AA; but the blind is maintained. Thirteen of 18 participants completed all study visits. Remaining participants have completed vaccination visits and at least 28 days of safety follow-up after M3 or M3M4 boost vaccination. The final study visit is scheduled for Jan 2025. Adverse events (AEs) following vaccination were mostly Grade I and resolved within 48 hours. One AE of special interest possibly related to the products was observed. No serious AEs occurred. ELISpot assays have been completed for 12 participants. Ten of the 12 participants exhibited strong increases in T-cell responses (>2 to 16-fold) to mosaic-1/2 immunogens at two weeks post M4 or M3M4 boosting. In most participants, HIV-1-specific T-cell breadth and the proportion of the total HIV-specific T-cell response targeting the HIVconsvX conserved regions increased after M4 or M3M4 vaccination. HIV-1-specific T-cell proliferation (CSFE) also consistently increased following vaccination.
Conclusions
We present the first results following vaccination with C62-M4 and C1C62-M3M4 in PWH on ART. Vaccination was safe and immunogenic. Analysis of unblinded safety and immunogenicity data for all study participants will be presented.
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