Dennis Hartigan-O'Connor
University of California-Davis, CA·Microbiology & Immunology
Vaccines work by teaching the immune system to recognize an invader, but for some viruses decades of effort have not produced a protective vaccine. Work here asks what makes an immune response good enough to stop or control a virus, focusing on two pathogens that are expert at evading immunity: HIV and cytomegalovirus (CMV), a common herpesvirus that can cause severe birth defects when a woman is first infected during pregnancy.
- Fields
Microbiology & Immunology
Medicine & Clinical Research
Biology
- Topics
HIV vaccine
therapeutic vaccine
broadly neutralizing antibodies
- Grants
- 7 known grants, through Nov 2029
What they work on
- Test whether partial-agonist IL-10 cytokines combined with mRNA vaccination can make HIV-specific T-cell responses unusually durable in macaques, including CXCR5+ follicular T cells that enter lymph-node sites where antibody-producing B cells mature.
- Selectively boost killer T cells of high avidity—those that sense viral peptide on infected cells most sensitively—by targeting their dependence on the CD8 co-receptor, and test whether such cells protect against SHIV infection.
- Determine how protein plus virus-like-particle vaccines aimed at HIV's Env fusion peptide interact with optimized T-cell vaccines, comparing simultaneous delivery against T-cell priming before the first B-cell vaccination.
- Track individual T-cell clones before and after therapeutic HIV/SIV vaccination using paired single-cell RNA and T-cell receptor sequencing with high-dimensional flow cytometry, asking whether vaccines recruit new clones with stem-like, TCF-1-high memory properties.
- Test whether metabolic signatures from plasma metabolomics, RNA sequencing, and SCENITH (a single-cell readout of which fuel a cell burns) predict T-cell breadth and control of virus after antiretroviral treatment is interrupted.
- Examine whether co-delivering SIV vaccines with supplemental arginine or with the arginine-destroying enzyme arginase 1 reshapes T-cell development through nutrient sensing and alters viremia after therapy stops.
- Compare CCR5 depletion and side effects of a CD3/CCR5 bispecific antibody made as a CrossMab versus by controlled Fab-arm exchange, to improve purity and safety before efficacy testing.
- Test whether depleting CCR5-expressing cells within days of starting antiretroviral therapy can induce durable SIV remission in infant macaques with limited viral replication, and whether adding a broadly neutralizing antibody helps when reservoirs are larger.
- Isolate B-cell clones from macaques protected against rhesus CMV to produce highly potent monoclonal antibodies that neutralize the virus-encoded IL-10 immune-damping protein.
- Determine whether passive transfer of viral IL-10 neutralizing antibodies, alone or with anti-glycoprotein B antibodies, protects rhesus macaques from naturally transmitted primary CMV infection.
More about the research
Projects span preventive HIV vaccines, therapeutic HIV vaccines meant to help people already infected, antibody-based strategies against CMV, and a cell-killing antibody designed to shrink the hidden pool of infected cells in infants. Most of the work uses rhesus macaques infected with monkey relatives of HIV (SIV and SHIV) alongside blood samples from vaccinated or infected people.
Why it matters
HIV has killed roughly 40 million people and still has no preventive vaccine and no cure. These projects could supply concrete tools: ways to generate longer-lived, more sensitive T cells to back up vaccine-induced antibodies, markers that explain why some people respond to therapeutic vaccines, and an antibody treatment that may push infants toward drug-free remission. The CMV work could lead to a preventive antibody given during pregnancy, which may reduce congenital CMV disease, and shows how targeting a virus's immune-evasion proteins could apply to other pathogens.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Contributions of durable, high-avidity T-cell responses to protection achieved using the Opti-FliP vaccine regimen
NIH · Dec 2024 – Nov 2029
Optimal T-cell support for HIV neutralizing antibody induction to fusion peptide-inclusive regimens (Opti-FliP)
NIH · Dec 2024 – Nov 2029
Understanding reservoir effects and curative potential of a CD3/CCR5 bispecific antibody in infant macaques
NIH · Aug 2024 – Jul 2029
Closest labs
Vijayakumar Velu
Emory University, GA·Microbiology & Immunology
Test how soluble IL-15/IL-15Rα-Fc, an immune-boosting cytokine complex, and galunisertib, a TGF-β pathway blocker, alone or combined, change T cell and natural killer cell subsets during chronic SIV infection in antiretroviral-treated rhesus macaques.
Matthew Gardner
Emory University, GA·Microbiology & Immunology
Test whether co-delivering an AAV vector encoding rhesus macaque PD-L1, a protein that engages the T-cell brake receptor PD-1, sustains blood levels of the HIV broadly neutralizing antibody 10-1074 high enough to protect macaques from repeated low-dose SHIV challenge.
Matthew R. Reynolds
University of Wisconsin-Madison, WI·Microbiology & Immunology
Determine how long virus takes to rebound after stopping antiretroviral therapy in rhesus macaques given defined reservoirs of 5x10^4, 1x10^4, 1x10^3 or 1x10^2 laboratory-generated, latently SIV-infected autologous cells.
The school
University of California-Davis: 49 labs on PI Pages, $1.0B a year on research, 647 research doctorates a year.
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