Combinatorial bnAb and T Cell Immunization Enhances Post-Infection Control of SHIV _SF162p3 Viremia in Rhesus Macaques

An ideal HIV-1 vaccine should provide broad protection against most HIV-1 variants, control early dissemination of infected cells after virus acquisition, and avoid the risk that vaccine-induced, HIV-specific CD4+ T cells serve as targets for viral transmission. In this study, we modeled this complex host-virus interaction in rhesus macaques challenged with a single high dose of SHIV _SF162p3 . Specifically, we evaluated the impact of T cell immunization with a human adenovirus-5-based candidate vaccine encoding an SIV Gag-Tat fusion (AdHu5 _SIVGag/Tat ) alongside a partially protective, limiting dose of the broadly neutralizing antibody (bnAb) PGT121. Immunization with AdHu5 _SIVGag/Tat elicited Gag-specific CD4+ and CD8+ T cell responses in PBMC and mucosal tissue. T cell vaccination did not affect PGT121-mediated protection against SHIV _SF162p3 acquisition. However, independently of vaccination, constitutively activated CD4+α4β7+Ki-67+ T cells in rectal tissue attenuated PGT121-mediated protection. Crucially, a unique pattern of post-infection control of SHIVSF162p3 viremia emerged in AdHu5 _SIVGag/Tat -immunized, PGT121-treated animals, characterized by an increased eclipse phase, lower peak viremia, and a late-phase decay in steady-state viremia. These results suggest potential synergy between bnAbs and AdHu5 _SIVGag/Tat -induced antiviral T cell responses, with significant implications for HIV-1 vaccine development and early interventions following infection.