Duke University supported with USD 1.17m from NIH for combined T cell and B cell HIV immunotherapy

Duke University has received a USD 1.17 million NIH R56 award from the National Institute of Allergy and Infectious Diseases to advance a combined T cell and B cell immunotherapy strategy aimed at achieving a functional cure for HIV-1 infection, with the project running through April 2027.

The grant, awarded to principal investigator Kevin O. Saunders in Duke’s Department of Surgery, funds preclinical work in SHIV-infected macaques alongside a translational human immune-profiling component. The core approach pairs a CD8 T cell countermeasure — delivered via an integrase-deficient lentiviral vector expressing the viral gag gene — with a B cell immunogen designed to elicit broadly neutralizing antibodies targeting the V2 Apex region of the HIV-1 envelope. In preliminary studies, each arm independently produced measurable antiviral activity in macaques; the funded work will test whether combining them produces durable viral suppression after antiretroviral therapy cessation.

The V2 Apex is a structurally conserved site on the HIV-1 envelope trimer recognized by several known human broadly neutralizing antibodies. Saunders and colleagues designed immunogens that elicit serum neutralizing antibodies with binding orientations similar to those human antibodies, a feature that supports cross-reactivity against heterologous viral strains. The CD8 T cell arm, delivered by the lentiviral vector, previously suppressed viremia to undetectable levels in macaques, providing the mechanistic basis for combining the two strategies.

A third aim introduces a human translational dimension: the team will use 10x Genomics BEAM-seq sequencing combined with machine learning to identify and characterize V2 Apex-specific B cells in people living with HIV before and during antiretroviral therapy. That component is designed to clarify how existing treatment affects the frequency and clonal composition of the B cell populations the immunogen strategy aims to engage, which has direct implications for how such a regimen might be sequenced in future clinical development.

The R56 mechanism is typically used by NIH to provide short-term support for research with strong preliminary data, often bridging toward a larger application. The one-year duration and direct cost level of USD 750,000 are consistent with that framing, though the NIH record does not specify the programmatic rationale. NIAID’s HIV Immunopathogenesis and Vaccine Development Study Section reviewed the award, reflecting the dual immunological and vaccine-adjacent nature of the approach.

Functional cure research has gained traction as a long-term goal alongside efforts to improve antiretroviral regimens, with several groups pursuing broadly neutralizing antibody combinations, latency reversal, and cell-based strategies. The Duke program is notable for its explicit combination of cellular and humoral immune arms tested in a controlled primate model with a defined ART cessation endpoint — a design that provides a cleaner read on durable virologic control than approaches relying on a single immune mechanism.

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