Compared with baseline, genital HSV-2 shedding rates immediately after dosing were reduced with GEN-003 (from 13.4% to 6.4% for 30 μg [.)Herpes simplex virus type 2 (HSV-2) is a common sexually transmitted pathogen that often causes recurrent genital lesions.
The findings may have implications for understanding other, more harmful pathogens that also exhibit latency, like varicella zoster, a herpes virus that causes chicken pox and shingles, and even tuberculosis and HIV. Cohen, MD, professor of ophthalmology who is leading a federally funded, multicenter study of varicella zoster infections of the eye, a potentially serious complication that can result in blindness and chronic pain.
“When these viruses come out of latency, they can cause many problems,” adds Dr.
If all goes well for the host, the immune system eventually overwhelms the virus and eliminates it.
But some viruses, including herpes simplex viruses, have evolved a clever tactic to linger on: a hibernation state known as viral latency, which allows viruses to lie dormant in a host’s cells, out of sight of the immune system.
But how viruses emerge from this sanctuary has been poorly understood, in part because it’s difficult to study ganglion cells in isolation.
“The ganglion is like a miniature organ,” explains Dr. “It contains many different types of cells, including immune cells.” The researchers’ solution was an innovative culturing technique “made of nothing but neurons,” says Dr. “It allows us to study the molecular signaling and circuitry in depth, without interference from other cells.” With a clear window onto the infected cells, the researchers made a startling discovery: when jostled awake by stress, HSV-1 bursts into action, releasing a flood of proteins that jams the host’s immune reaction to interferon signals from infected cells, effectively disarming the cells’ alarm system.
“This happens in the very first instant that HSV-1 reactivates,” explains Angus C.
Wilson, Ph D, an associate professor of microbiology and another of the paper’s coauthors.
Preclinical studies have demonstrated that GEN-003 elicits antibody and T-cell responses in mice and is protective in a guinea pig model of recurrent HSV-2 infection .
We conducted a double-blind, placebo-controlled, dose-escalation phase 1/2 study of GEN-003 to evaluate the safety, immunogenicity, and effect on viral shedding of this candidate immunotherapy (clinical trials registration NCT01667341).