Ad26/MVA Therapeutic Vaccination with TLR7 Stimulation in SIV-Infected Rhesus Monkeys

The development of immunologic interventions that can target the viral reservoir in HIV-1-infected individuals is a major goal of the HIV-1 cure field(1,2). However, little evidence exists that the viral reservoir can be sufficiently targeted to improve virologic control following discontinuation of antiretroviral therapy (ART). Here we show that Ad26/MVA(3,4) therapeutic vaccination with toll-like receptor 7 (TLR7) stimulation improves virologic control and delays viral rebound following ART discontinuation in SIV-infected rhesus monkeys that initiated ART during acute infection. Ad26/MVA therapeutic vaccination resulted in a dramatic increase in the magnitude and breadth of SIV-specific cellular immune responses in virologically suppressed, SIV-infected monkeys. TLR7 agonist administration led to innate immune stimulation and cellular immune activation. The combination of Ad26/MVA vaccination and TLR7 stimulation resulted in decreased levels of viral DNA in lymph nodes and peripheral blood, as well as improved virologic control and delayed viral rebound following ART discontinuation. Cellular immune breadth correlated inversely with setpoint viral loads and correlated directly with time to viral rebound. These data demonstrate the potential of therapeutic vaccination with innate immune stimulation as a strategy aimed at an HIV-1 functional cure.