Matthew Gardner
Emory University, GA·Microbiology & Immunology
Daily antiviral pills keep HIV in check but never clear it, because a hidden pool of infected cells, the viral reservoir, persists for life. An alternative is to make the body produce its own long-lasting HIV-blocking proteins.
- Fields
Microbiology & Immunology
Medicine & Clinical Research
Biomedical Engineering
- Topics
broadly neutralizing antibodies
bNAbs
eCD4-Ig
- Grants
- 3 known grants, through Jan 2031
What they work on
- 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.
- Engineer AAV transgene cassettes and evaluate a new AAV capsid, and test dose-reduction strategies, to raise antibody expression from a single intramuscular injection in macaques.
- Assess whether AAV-delivered eCD4-Ig, an entry inhibitor that neutralizes all tested HIV-1, HIV-2 and SIV isolates, combined with the antibody 10-1074 keeps SHIV suppressed in macaques after antiretroviral therapy is withdrawn.
- Compare the size of the viral reservoir in macaques suppressed by AAV-delivered eCD4-Ig plus 10-1074 against reservoirs in animals suppressed by antiretroviral drugs.
- Build an irreversible genetic kill-switch that permanently turns off AAV transgene expression, improving the safety of AAV-delivered antibody gene therapy.
- Optimize AAV delivery of multiple SIV broadly neutralizing antibodies with eCD4-Ig and determine whether drug-free, antibody-mediated suppression speeds the decay of the SIV reservoir relative to antiretroviral therapy.
More about the research
Work in this lab uses adeno-associated virus (AAV) vectors, harmless gene-delivery viruses, injected once into muscle so that muscle cells secrete broadly neutralizing antibodies (bNAbs, antibodies that block many HIV strains) and antibody-like entry inhibitors for months to years. Across projects the lab tackles the main obstacles to this strategy in rhesus macaques: the host immune system attacking the delivered protein or the vector, whether such proteins can prevent infection, and whether they can shrink the reservoir in ways daily drugs cannot.
Why it matters
Lifelong daily antiretroviral therapy is costly, hard to maintain, and leaves the HIV reservoir intact. A single intramuscular injection that makes the body produce HIV-blocking antibodies and eCD4-Ig could offer durable prevention for people at high risk, including people who inject drugs, and a drug-free way to suppress infection. Because these proteins can also kill infected cells, the work may show whether they shrink the reservoir faster than drugs, a step toward HIV cure strategies, while the kill-switch addresses gene therapy safety.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
James Termini
University of Miami, FL·Microbiology & Immunology
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.
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.
Wei Li
University of Pittsburgh, PA·Microbiology & Immunology
Engineer soluble CD4 D1-domain variants with improved binding kinetics and isolate single-domain VH binders against CD4-induced epitopes on HIV envelope, combining computational structure design, phage display and time-resolved cryo-electron microscopy.
The school
Emory University: 70 labs on PI Pages, $1.2B a year on research, 286 research doctorates a year.
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