Therapeutic efficacy of combined active and passive immunization in ART-suppressed, SHIV-infected rhesus macaques.
Victoria E K Walker-SperlingNoe B MercadoAbishek ChandrashekarErica N BorducchiJinyan LiuJoseph P NkololaMark G LewisJeffrey P MurryYunling YangRomas GeleziunasMerlin L RobbNelson L MichaelMaria G PauFrank WegmannHanneke SchuitemakerEmily J FrayMithra R KumarJanet D SilicianoRobert F SilicianoDan H BarouchPublished in: Nature communications (2022)
The latent viral reservoir is the critical barrier for developing an HIV-1 cure. Previous studies have shown that therapeutic vaccination or broadly neutralizing antibody (bNAb) administration, together with a Toll-like receptor 7 (TLR7) agonist, enhanced virologic control or delayed viral rebound, respectively, following discontinuation of antiretroviral therapy (ART) in SIV- or SHIV-infected rhesus macaques. Here we show that the combination of active and passive immunization with vesatolimod may lead to higher rates of post-ART virologic control compared to either approach alone. Therapeutic Ad26/MVA vaccination and PGT121 administration together with TLR7 stimulation with vesatolimod resulted in 70% post-ART virologic control in SHIV-SF162P3-infected rhesus macaques. These data suggest the potential of combining active and passive immunization targeting different immunologic mechanisms as an HIV-1 cure strategy.