University of California, Irvine immunologist Lbachir BenMohamed has been awarded a $3.93 million National Institutes of Health grant to develop and test a novel therapeutic vaccine designed to prevent recurrent genital herpes, a lifelong viral infection that affects more than 60 million Americans and over 530 million people worldwide.

Low-Grade_Papillary_Urothelial_Tumor_of_Bladder_with_Herpes_Simplex_Virus_Infection_(8534832864)

Source: Ed Uthman from Houston, TX, USA

HSV types 1 & 2 immunostain.

The five-year R01 NIH award will support research on a next-generation vaccine strategy that could provide long-lasting protection against recurrent outbreaks of herpes simplex virus type 2, the leading cause of genital herpes. The project, titled “A Novel Prime/Pull/Keep Vaccine to Prevent Recurrent Genital Herpes,” builds on years of research conducted by BenMohamed and his collaborators.

“Despite decades of research, people living with recurrent genital herpes still have no therapeutic vaccine option,” said BenMohamed, professor of immunology and director of the Laboratory of Cellular and Molecular Immunology in the UC Irvine School of Medicine. “This award allows us to advance an innovative immune-based strategy that not only boosts protective T cells but directs them to the tissues where the virus hides and reactivates.”

“Our goal is to develop a safe and durable therapeutic vaccine that can reduce recurrent disease, limit transmission, and ultimately improve the lives of millions of people worldwide,” he added.

Tissue-resident memory T-cells

Unlike traditional vaccine approaches that primarily stimulate antibody responses, the new strategy is designed to strengthen and sustain specialized immune cells known as tissue-resident memory T cells at the sites where HSV-2 establishes lifelong infection. The vaccine’s “Prime/Pull/Keep” approach works by first priming protective immune cells, then directing them to infected tissues, and finally maintaining them there to provide long-term immune surveillance.

BenMohamed’s team has already generated promising preclinical results. Previous studies demonstrated that therapeutic mRNA vaccine candidates reduced recurrent genital herpes in animal models and boosted protective immune responses in tissues where the virus establishes lifelong infection. Additional research showed that targeted immune-signaling molecules could recruit and maintain protective T cells in those tissues, further improving protection.

The new NIH-funded project will evaluate the safety and effectiveness of Prime/Pull/Keep vaccine candidates in preclinical models and investigate how increasing the number, function, and longevity of tissue-resident immune cells correlates with protection against recurrent disease.

“Results from the preclinical studies of the Prime/Pull/Keep vaccine candidates will identify the best candidate vaccine, paving the way for future clinical trials,” said BenMohamed. “This will bring us closer to a long-sought therapeutic vaccine capable of reducing recurrent outbreaks and limiting transmission of HSV-2. The project aligns with NIH priorities to develop new therapeutic strategies for genital herpes.”

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