Identification and elimination of antigen-specific expanded clones - clonal expansion is a process where latently infected CD4+ t cells proliferate in response to their cognate antigen

The National Institute of Allergy and Infectious Diseases awarded The Johns Hopkins University $427,438 under Project Grant R21AI195115 on April 1, 2026, for research on identification and elimination of antigen-specific expanded clones in HIV latency.

The research investigates clonal expansion of latently infected CD4+ T cells in response to cognate antigen, a process believed to contribute substantially to HIV reservoir size. The award funds a two-step intervention strategy: vaccination of individuals with cognate antigen paired with short-term treatment using chemotherapeutic or antiproliferative agents to selectively eliminate dividing antigen-specific CD4+ T cells. The approach derives from observations of significant decline in expanded CD4+ T cell clones in an elite suppressor who received chemoradiation for lung cancer, with in vitro recapitulation of this effect using patient-derived CD4+ T cells stimulated by cognate antigen combined with antiproliferative agents. If successful across additional individuals, the strategy may reduce the size of the latent HIV reservoir.

Performance occurs in Baltimore, Maryland, with a period of performance from April 1, 2026 through March 31, 2028. Funding is provided through the Allergy and Infectious Diseases Research program (CFDA 93.855), which supports biomedical research and research training in infectious diseases and related areas at public and private nonprofit institutions.

IT is thought that this process contributes significantly to the size of the HIV reservoir and therefore disrupting this mechanism could have a huge impact on the number of latently infected cells. We observed a significant decline in the number of expanded CD4+ t cell clones in an elite suppressor who received chemoradiation for lung cancer and have shown that we can recapitulate this in vitro by stimulating CD4+ t cells from this patient with a combination of cognate antigen to induce proliferation, and either chemotherapeutic or antiproliferative agents to selectively kill the dividing antigen-specific CD4+ t cells. If successful in other individuals, a two- step process of vaccination of individuals with cognate antigen and short-term treatment with chemotherapeutic or antiproliferative agents may be part of a strategy to reduce the size of the reservoir.