Groundbreaking research on how our immune system develops and responds to chronic infections

Dennis Hartigan-O’Connor leads groundbreaking research in immunology, infectious disease, and regenerative medicine. His work focuses on understanding the orchestrated action of the adaptive immune system in controlling infections.

A central theme of his research is understanding how T-cell responses are shaped by metabolic factors and how they contribute to protective immunity. His lab investigates how different populations of immune cells—like Th17 cells and regulatory T cells (T-regs)—develop and respond to infections, inflammation, and environmental cues. These insights are especially relevant in the context of HIV and SIV (simian immunodeficiency virus), as well as CMV (cytomegalovirus), where T cells make an important but still poorly understood contribution to controlling the infections.

Hartigan-O’Connor’s funded projects in FY 2025 include advanced studies on SARS-CoV 2 prophylaxis, as well as preclinical efforts to prevent CMV and HIV infections, and to push HIV into remission by ablating cells that harbor the virus. 

He is PI of the collaborative OPTI-FliP prophylactic HIV vaccine project, which received over $3.5 million in NIH funding in FY 2025. The OPTI-FliP team is working to develop a new kind of HIV vaccine that relies on teamwork between specific antibodies and optimally conditioned T cells. The goal is to develop a preventative vaccine that keeps the virus from entering the body and establishing a permanent infection. 

Hartigan-O’Connor is also a PI of the study “Multi-omic understanding of the transformed host T-cell response to HIV following therapeutic vaccination.” This study is looking for solutions to the limited success of candidate HIV vaccines in clinical trials for the therapy of people who were already infected. This research team postulates that the poor results stem from the tendency of a therapeutic vaccine to further expand anti-HIV immune cells that are already exhausted by chronic infection. The team is exploring which features of the vaccine and host might allow therapeutic vaccination to elicit a superior immune response that may control the HIV virus after daily antiretroviral therapy is stopped.

Major Awards FY 2024-2025:

  • HIV FP Cocktail Vaccines Designed for Optimal Follicular T and B Cell Induction and Efficacy (Opti-FliP)
  • Multi-omic Understanding of the Transformed Host T-cell Response to HIV Following Therapeutic Vaccination
  • Phase 1/2a Study of a Tfh-Targeting Genetic Adjuvant Designed to Induce Broad, Durable Immune Responses to SARS-CoV-2
  • Prevention of CMV Infection with a Viral IL-10 Neutralizing Antibody
  • Understanding Reservoir Effects and Curative Potential of a CD3/CCR5 Bispecific Antibody in Infant Macaques.