Ad26 Based Therapeutic Vaccines for HIV

The goal of therapeutic vaccination is to increase host immune control of HIV-1 to achieve durable virologic
control in the absence of ART, which is defined as a “functional cure”. However, therapeutic vaccine studies in
humans have to date been largely unsuccessful. We speculate that this may reflect the fact that prior vaccines
(i) have failed to induce sufficient breadth of cellular immune responses and (ii) have not effectively activated or
targeted the latent viral reservoir. We hypothesize that a therapeutic vaccine that induces potent and broad
immune responses and that activates the latent viral reservoir will reduce the size of the replication-
competent viral reservoir and will enhance virologic control following ART discontinuation.
We have shown that Ad26/MVA therapeutic vaccination together with innate immune stimulation with a TLR7
agonist resulted in virologic control in a subset of SIV-infected rhesus monkeys following ART discontinuation.
We therefore propose to evaluate the immunogenicity and efficacy of the Ad26/MVA + TLR7 agonist vaccine in
HIV-1-infected humans to define its ability to control viral replication following discontinuation of ART.
We also hypothesize that the addition of broadly neutralizing antibodies (bNAbs) may augment the antiviral
efficacy of a therapeutic vaccine. To optimize both active and passive immunity, we propose a follow-up study
to evaluate the optimal therapeutic vaccine together with bNAbs in HIV-1-infected humans.
We therefore propose the following two Specific Aims:
Specific Aim 1. To evaluate the safety, immunogenicity, and efficacy of Ad26/MVA therapeutic
vaccination with TLR7 agonist administration in HIV-1-infected humans
Specific Aim 2. To evaluate the safety, immunogenicity, and efficacy of Ad26/MVA therapeutic
vaccination with broadly neutralizing antibodies (bNAbs) and a TLR7 agonist in HIV-1-infected humans

Grant Number: 5U01AI145801-06
NIH Institute/Center: NIH
Principal Investigator: Dan Barouch