Research Goals

The goal of the CIAVCR program is to develop an effective combined immunotherapeutic regimen for HIV-1 prevention and cure using the nonhuman primate (NHP) model that will have a direct path to clinical applications. The goal is to build upon the vaccine strategy already proved to induce protective immune responses in NHP models by exploring innovative mRNA constructs for immunogen delivery that can elicit both protective and therapeutic B and T cell responses. 

The Objectives of the Duke CIAVCR program

The Duke CIAVCR program is organized by two Research FOCI critical to advance efforts toward HIV-1 control and eradication using HIV-1 vaccination strategies and novel immunotherapeutics. By successfully achieving our objectives, we will also make groundbreaking discoveries, and develop new research platforms and paradigms to accelerate progress towards creating a functional cure for HIV-1 infection:

In FOCUS 1, our overall goal is to demonstrate the correlates and mechanisms of protection for a protective vaccine. We will also evaluate the benefits of using mRNA constructs to deliver immunogens that can elicit both humoral and cellular responses.

In FOCUS 2, our overall goal is to determine the role of vaccine-induced immune responses to 1) control HIV-1 infection by reducing the size or eliminating HIV-1 reservoirs, and/or 2) delay plasma virus load rebound. The protective vaccines studied in FOCUS 1 will be tested to define the mechanisms of vaccine-induced B and T cell responses in clearing HIV-1 reservoirs when the regimens are implemented during the chronic and acute phase of infection.

Additionally, novel Ab-based immunotherapies will be combined with the vaccines to augment clearance of HIV-1 reservoirs.

In both FOCUS 1 and 2, analysis of the breakthrough and latent reservoir Env sequences will inform the design of new vaccine boosts for an improved protective vaccine regimen that can also limit rebound viruses.

The NHP-SHIV Centralized Research Resource (CRR) supports the NHP studies in FOCUS 1 and 2 to investigate the effectiveness of vaccine-induced polyfunctional responses and novel immunotherapies in clearing HIV-1 reservoirs. These studies use innovative barcoded-SHIVs to determine the effect of vaccine-induced responses on eliminating the viral reservoirs, and to evaluate the quantity and quality of viruses that are reactivated by latency reversing agents (LRAs) following treatment interruption.