Research

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Uncovering the path to sustained HIV remission

An essential question for HIV cure research is: how small must HIV reservoirs be to achieve sustained remission without antiretroviral drugs? While antiretroviral therapy (ART) effectively controls HIV replication, it’s not a cure. Therefore, significant efforts are focused on developing treatments to reduce viral reservoirs and enhance antiviral immunity. The critical challenge remains: exactly how small must these viral reservoirs become to allow patients to safely discontinue ART? To address this fundamental question, we developed an innovative model to precisely control the size of latent reservoirs in rhesus macaques. This model helps us understand the impact of small viral reservoirs on the timing of viral rebound and whether antiviral immune responses can effectively control virus replication after ART withdrawal.

Our research will hopefully bring us closer to defining a threshold for HIV remission—a crucial step toward developing strategies that may one day free patients from lifelong ART.

Antibody discovery

We pioneered a novel SMART-RACE-based approach to cloning antibodies from individual rhesus macaque B cells. Unlike traditional PCR methods that struggle with diversity in immunoglobulin leader sequences, our technique eliminates the need for complex multiplex primer sets, improving recovery rates from single cells. 

With this method, we isolate monoclonal antibodies targeting specific host proteins, including macaque major histocompatibility complex (MHC) and killer-immunoglobulin-like receptor (KIR) molecules. Our anti-MHC antibodies are available through the Nonhuman Primate Reagent Resource.

Need custom antibodies for your research? We offer comprehensive isolation services through the WNPRC Immunology Services unit. Our versatile method can work with virtually any species—from mice and primates to non-traditional animal models like ferrets, hamsters, dogs, and pigs—helping researchers develop novel reagents for diverse applications.

Mapping minor histocompatibility antigens

Minor histocompatibility antigens (mHAgs) are MHC-bound peptides on cell surfaces that can stimulate immune responses after organ transplants resulting from genetic differences between organ donors and recipients. Identifying mHAgs is challenging due to the vast genomic landscape and countless genetic variations between individuals.

We developed an innovative process to map mHAg in Mauritian cynomolgus macaques using a powerful combination of cellular immunology, genomics, and bioinformatics. Using this approach, we identified the first nonhuman primate mHAg., which serves as a model antigen for testing mHAg-targeted therapies for blood-borne cancers and advancing HIV cure strategies in macaques.