James Termini
University of Miami, FL·Microbiology & Immunology
One promising route to long-term HIV control skips vaccination entirely: instead of asking the body to make its own protective antibodies, engineers deliver the gene for a ready-made antibody and let muscle cells manufacture it for years. The carrier is adeno-associated virus (AAV), a harmless virus repurposed as a gene-delivery vehicle, and the cargo is a broadly neutralizing antibody (bNAb), a rare human antibody that blocks a wide range of HIV strains.
- Fields
Microbiology & Immunology
Medicine & Clinical Research
Biology
- Topics
broadly neutralizing antibodies
bNAbs
adeno-associated virus
- Grants
- 1 known grant, through Jun 2031
What they work on
- Build and validate engineered probiotic strains that survive oral delivery and colonize the gut, with Bifidobacterium longum secreting functional immunoadhesins derived from the HIV antibodies 3BNC117 and 10-1074.
- Engineer Lactococcus lactis to secrete IL-10, an immune-calming signaling molecule, and test whether it strengthens tolerogenic signaling that supports oral tolerance to the delivered antibodies.
- Test in rhesus macaques whether weekly oral probiotic pretreatment before intramuscular AAV9 delivery prevents anti-drug antibody responses, induces regulatory T cells, and extends durable bNAb expression, compared with feeding purified antibody.
- Determine whether sustained probiotic exposure can reprogram humoral immunity that has already formed against the delivered antibodies and restore expression after AAV delivery.
- Evaluate probiotic-induced oral tolerance in SHIV chronically infected macaques on antiretroviral therapy, a setting with ongoing immune inflammation, to test clinical relevance.
More about the research
This approach has worked strikingly well in monkeys, but it has one persistent failure mode: the recipient's immune system treats the delivered antibody as foreign and mounts an anti-drug antibody response that shuts expression down. This project attacks that barrier using the gut.
Why it matters
If gut bacteria can teach the immune system to accept a delivered antibody, people living with HIV could receive long-lasting antibody protection from a single gene-delivery injection without lifelong daily antiretroviral pills, and uninfected people at risk could gain durable prevention. Because the method is microbiome-based rather than broadly immunosuppressive, it may also extend the lifespan of AAV-delivered biologics for other diseases.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
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.
Dennis Hartigan-O'Connor
University of California-Davis, CA·Microbiology & Immunology
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.
Aravind Asokan
Duke University, NC·Biomedical Engineering
Test whether IceMG, an engineered protease that cleaves human and monkey IgG and IgM antibodies, blocks complement activation and modulates B-cell signaling, using human cell models, humanized mice and non-human primates.
The school
University of Miami: 30 labs on PI Pages, $559M a year on research, 297 research doctorates a year.
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