Finally: A vaccine for herpes simplex

Brett Smith for – @ParkstBrett

From polio to smallpox, vaccines have gone a long way in eradicating many of the world’s diseases, but some viruses remain stubbornly untreatable with vaccines.

The herpes simplex virus is one of those viruses currently without an effective vaccine, and researchers at the Howard Hughes Medical Institute (HHMI) in Chevy Chase, Maryland have recently announced the development of a promising new candidate that was developed through unconventional logic.

According to a report published in the journal eLife, the vaccine was developed by essentially overlooking the most obvious target – a protein on the virus’ surface called glycoprotein D (gD-2).

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“We have a very promising new candidate for herpes,” said study author William Jacobs, an HHMI investigator at the Albert Einstein College of Medicine, “but this might also be a good candidate as a vaccine vector for other mucosal diseases, particularly HIV and tuberculosis.”

A G-D vaccine

The new vaccine was found to work against the two most typical forms of herpes that cause cold sores (HSV-1) and genital ulcers (HSV-2). Both viruses infect the body’s nerve cells, where they can sit inactive for years until symptoms come back. The new vaccine is the first to counteract this kind of dormant infection.

“With herpes sores you continually get them,” Jacobs said. “If our vaccine works in humans as it does in mice, administering it early in life could completely eliminate herpes latency.”

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Earlier attempts to develop a herpes vaccine have centered on gD, a protein that allows the pathogen to pass in and out of cells, as well as spread from cell-to-cell. The protein also solicits a strong antibody response a large number of experts in the field believe is needed to create immunity. However, previous work on a gD-based vaccine has not proven effective.

“It was necessary to shake the field up and go another route,” said study author Betsy Herold, a virologist and infectious disease physician at the Albert Einstein College of Medicine.

To work around gD, the study team engineered a version of the virus without that protein.

“Once we had this mutant in our hands,” Herold said, “it was a logical, scientifically driven hypothesis to say, ‘This strain would be 100 percent safe and might elicit a very different immune response than the gD subunit vaccines that have been tried.’”

Once the team was able to deliver an HSV-2 virus without gD into a cell line, it replicated abundantly in the cells, but was unable to infect new cells because it lacked that key protein. The team watched as the infected cells became “little factories for making viral proteins” that spurred the immune system to produce antibodies to HSV-2, Harold said.

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The vaccine totally immunized two typical strains of lab mice against HSV-2 when tested with virus intra-vaginally or on the epidermis. The team also could not detect the virus in vaginal washes four days after the test and, more importantly, virus was not found in nerve tissue, where HSV often hides in a dormant form. Protection against HSV-1, which shares substantial homology with HSV-2, was also shown in both models. The vaccine created no adverse health effects in a group of mice with seriously jeopardized immune systems, showing the vaccine’s overall safety.

The team speculated that gD, which brings about a strong immune response, may actually overwhelm the immune system, causing it to “not see” other components of the virus that could be targeted.

“Herpes is a pretty smart little virus,” Herold said. “It has multiple immune evasion strategies and this is one of many.”


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