Title: Combinatorial bnAb and T Cell Immunization Enhances Post-Infection Control of SHIVSF162p3 Viremia in Rhesus Macaques

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.

doi:10.64898/2026.11.04.764342

bioRxiv · 10.64898/2026.11.04.764342

Title: Combinatorial bnAb and T Cell Immunization Enhances Post-Infection Control of SHIVSF162p3 Viremia in Rhesus Macaques

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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Abstract

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.

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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.. 2026-11-05. Title: Combinatorial bnAb and T Cell Immunization Enhances Post-Infection Control of SHIVSF162p3 Viremia in Rhesus Macaques. https://doi.org/10.64898/2026.11.04.764342

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