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. 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. Project Number: 1R21AI195115-01A1 | Fiscal Year: 2026 | NIH Institute/Center: National Institute of Allergy and Infectious Diseases (NIAID) | Principal Investigator: JOEL BLANKSON | Institution: JOHNS HOPKINS UNIVERSITY, BALTIMORE, MD | Award Amount: $427,438 | Activity Code: R21 | Study Section: HIV Immunopathogenesis and Vaccine Development Study Section[HIVD] View on NIH RePORTER: https://reporter.nih.gov/project-details/1R21AI19511501A1