Prime/Pull/Keep therapeutic vaccines

What Prime/Pull/Keep is

Prime/Pull/Keep is a strategy, not a single vaccine. It comes from the laboratory of Lbachir BenMohamed at the University of California, Irvine, and aims to treat people who already have herpes (a therapeutic approach) rather than to prevent infection. HSV hides in nerve cells, in clusters called ganglia, and periodically reactivates. The idea is to place T cells, immune cells that find and kill infected cells, where the virus reactivates.

The three steps are described in the papers this way. Prime is a vaccine that teaches T cells to recognize HSV. Pull is a second treatment, an engineered virus carrying a chemokine (a signaling protein that attracts immune cells), such as CXCL11, that draws T cells into the ganglia and the mucosa. Keep adds immune-signaling proteins (IL-2 and IL-15 in the rabbit study) intended to help the T cells stay.

The antigens, the parts of HSV used to teach the immune system, are not the same across the papers. The 2019 and 2024 guinea-pig papers use a protein called ribonucleotide reductase 2 (RR2). The 2025 guinea-pig paper uses adenovirus-based vaccines carrying RR2 and glycoprotein D (a surface protein the virus uses to enter cells). The 2025 rabbit paper uses 13 short peptides (protein fragments) from HSV-1 proteins, delivered by an AAV8 vector, a harmless engineered virus used as a delivery vehicle. Results for one version should not be read as results for another.

Where Prime/Pull/Keep stands

All published results are from animals. In the HSV-2 guinea-pig studies the animals were infected first and treated afterward. The 2019 paper reports that RR2 protein reduced virus shedding and the severity and frequency of recurrent genital lesions. The 2024 paper reports that RR2 plus a CXCL11 “pull” step increased T-cell numbers in the ganglia and vaginal tissue and reduced recurrences compared with RR2 alone. The March 2025 paper reports that adenovirus vaccines carrying RR2 or glycoprotein D reduced shedding and lesions.

The April 2025 paper tested the full three-step version in HLA-A*0201 transgenic rabbits (rabbits engineered to carry a human immune-system gene) infected in the eye with HSV-1. The authors report T cells accumulating in the trigeminal ganglion and a significant reduction in corneal infection and disease.

The sources cited here run through April 2025. A ClinicalTrials.gov search on 2026-10-22 for “BenMohamed”, “prime pull keep herpes” and “rAd-RR2” returned no records. We could not reach a funder record (such as NIH RePORTER) from our environment, so this page states no grant. We found no primary source for a company, a regulatory filing or a planned human trial, so none is stated here.

What this does and doesn’t mean for Prime/Pull/Keep

These are guinea-pig and rabbit results, and the outcomes measured are lesions, virus shedding and T-cell counts in animals. They do not show that any version of the strategy would reduce recurrences in people. Guinea-pig results are for HSV-2 and the rabbit results are for HSV-1 eye disease, so they are not interchangeable. Because the antigens and vectors change between papers, there is no single product to compare with other candidates. No safety data in people exist for it.