Title: Combinatorial bnAb and T Cell Immunization Enhances Post-Infection Control of SHIVSF162p3 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 SHIVSF162p3. Specifically, we evaluated the impact of T cell immunization with a human adenovirus-5-based candidate vaccine encoding an SIV Gag-Tat fusion (AdHu5SIVGag/Tat) alongside a partially protective, limiting dose of the broadly neutralizing antibody (bnAb) PGT121. Immunization with AdHu5SIVGag/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 SHIVSF162p3 acquisition. However, independently of vaccination, constitutively activated CD4+4{beta}7+Ki-67+ T cells in rectal tissue attenuated PGT121-mediated protection. Crucially, a unique pattern of post-infection control of SHIVSF162p3 viremia emerged in AdHu5SIVGag/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 AdHu5SIVGag/Tat-induced antiviral T cell responses, with significant implications for HIV-1 vaccine development and early interventions following infection.

Carnathan, D. G., Enemuo, C. A., Ngo, J. T., Jimenez, L. E., Choe, Y., Silverman, J. B., Ciupe, S., Silvestri, G., Kasturi, S. P., Gallo, R. C., Lewis, G. K.

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