Herpes Vaccine Performs Well in Preclinical Trials

Millions of individuals are infected with herpes simplex virus 2, which is better known as genital herpes. Despite many attempts to create an effective preventative treatment, no candidate vaccine has performed well in clinical trials.

However, a new study published by PLOS Pathogens found that a novel candidate vaccine can provide protection against herpes infections in guinea pig and monkey models.

The newly-created trivalent vaccine provides protection against 3 components of the virus, 2 of which help the herpes simplex virus 2 (HSV2) evade attack from the immune system.

“It’s a novel strategy, and it works beautifully,” said senior investigator Harvey M. Friedman, MD. “I know of no other HSV2 vaccine candidate with published results that are as promising as this study.”

The authors said that these positive findings will likely lead to clinical trials of the candidate vaccine.

In the United States alone, approximately 1 in 6 individuals aged 15 to 49 are suspected to have a herpes infection. In some African countries, more than half of adults have the infection, according to the study.

Besides the health effects of the infection on the host, herpes infections can cause deathly infections of infants born to mothers with the virus. Additionally, HSV2 also increases the risk of HIV transmission, which adds to the burden of HIV as well.

Other candidate herpes vaccines have focused on solely targeting the glycoprotein gD2 that is affixed to the virus’ outer membrane, which allows the virus to infiltrate healthy cells. Unfortunately, these candidate vaccines have not been observed to provide strong protection in animal and human trials.

In the new study, the researchers created a vaccine that would create an immune response against gD2, along with 2 other viral glycoproteins, gC2 and gE2. The 2 new additions to the vaccine are known to inhibit immune response, and allows the virus to survive in the host, according to the study.

“In essence, we’re stimulating the immune system to attack the virus and at the same time preventing the virus from using some of the tools it has to thwart that immune attack,” Dr Friedman said.

In the preclinical trials, when the vaccine is given 3 times at monthly intervals, it showed a strong immune response in macaque monkeys. This immune response resulted in antibodies against the 3 viral glycoproteins in blood and vaginal secretions, according to the study.

In lab experiments, the antibodies were seen to inhibit the herpes virus from spreading. An increase in CD4 T cells was also seen, which is important since these cells mobilize the immune response against infection.

The researchers also discovered that the antibodies elicited by the vaccine neutralized 4 isolates of the virus from sub-Saharan Africa, where the infections are widespread, according to the study.

Typically, macaques do not develop genital lesions after infection, but in the study, control animals displayed symptoms of slight vaginal inflammation, while vaccinated monkeys were not observed to be affected.

The researchers found that vaccinated guinea pigs, which typically develop a severe genital infection from HSV2, were protected against genital lesions. However, small amounts of herpes DNA were detected in genital secretions, but only a small portion was capable of replicating, according to the study.

In theory, the vaccine virtually eliminated the virus’ ability to spread.

"We are pleased to have demonstrated such a potent and durable immune response to the vaccine,” said study lead author, Sita Awasthi, PhD. “If found effective in clinical trials, the vaccine will have a huge impact on reducing the overall prevalence of genital herpes infections and could reduce new HIV infections as well, especially in high-burden regions of sub-Saharan Africa.”

The investigators are now working with pharmaceutical manufacturers to move the vaccine into clinical trials. If successful, individuals would be given the vaccine at 0, 1, and 6 months, according to the study.

“If the vaccine behaves like this in people, it would limit lesions to appearing only about one day in 100, and the virus would be potentially contagious only about two in every 1,000 days,” Dr Friedman concluded.