Genital HSV Vaccine Provides Powerful Protection in Preclinical Trials


Researchers have developed a new trivalent vaccine that has proven to provide powerful protection against genital herpes (HSV) in preclinical trials.

Around the world, about half a billion individuals are infected with herpes simplex virus type 2 (HSV-2), the virus that most commonly causes genital herpes. With a number this staggering, researchers around the world have been channeling their efforts into the development of a safe and effective vaccine that will put an end to this global pandemic once and for all.

None of the past vaccine candidates have been successful, but a new trivalent vaccine coming from scientists at the Perelman School of Medicine at the University of Pennsylvania may be the one that will change it all. In preclinical tests, the trivalent vaccine—which produces antibodies that fight three different parts of the virus—proved to provide “powerful protection” in preclinical trials, according to a recent press release.

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

It is estimated that about one in six individuals who are between the ages of 15 and 49 are plagued by genital herpes, and this is just in the United States. On a grander scale, there are countries that have been hit particularly hard with the virus, such as Africa, where it is estimated that about half of the adult population is infected. In some adults, these infections result in genital lesions, or ulcers, and they can be particularly painful, while in others the infection may remain dormant, according to the study. Anyone who is infected has the potential to transmit the virus to others, and in fact, the infection is reported to “increase the likelihood of HIV transmission.”

Many of the vaccine candidates that were developed in the past targeted a glycoprotein called gD2, which would attach to the outer envelope of the virus and assist the virus in getting into the host cells. Although on the right track, researchers found that targeting gD2 alone didn't provide the desired amount of protection. Dr. Friedman told Contagion®, "The prior gD2 vaccine did show good effectiveness in animal models but not as good in humans."

Therefore, Dr. Friedman and his team decided to take an alternative approach by creating a trivalent vaccine that would target two other viral glycoproteins—gC2 and gE2—in addition to gD2. These two glycoproteins have been known to block immune response, which would allow HSV2 to persist within its hosts long-term.

When speaking with Contagion® on how this vaccine is different, Dr. Friedman explained, "Our vaccine builds upon the protection provided by the gD2 protein. We have taken the approach of adding two other proteins, glycoprotein C (gC2) and glycoprotein E (gE2). The virus uses gC2 and gE2 to escape immune attack. By including these proteins in the vaccine, antibodies made to the proteins block the ability of the virus to escape immune attack, including the immune attack generated by the vaccine."

To test the new vaccine, the researchers teamed up with the Tulane National Primate Center in Louisiana to see how the vaccine would fare in macaque monkeys, because their immune system is similar to that of a human’s. Dr. Friedman and his team administered the trivalent vaccine “three times at monthly intervals” and found that it induced a strong immune response against all three of the glycoproteins in both blood and vaginal secretions. When analyzed in a lab dish, the researchers found that the antibodies were able to neutralize the virus, preventing its spread throughout the cells. In addition, the researchers noted a “sharp rise in CD4 T-cells, whose job it is to mobilize the antibody response and other immune elements against viral infections.” Furthermore, they found that the antibodies were able to neutralize four HSV2 isolates that are from sub-Saharan Africa.

The study authors noted that although it is not typical for macaques to develop genital lesions as a result of HSV2 infection, some of the monkeys that did not receive the vaccine did exhibit minor vaginal inflammation. In contrast, the macaques that were vaccinated did not present with any vaginal inflammation.

Taking it a step further, the researchers decided to test the vaccine on guinea pigs, which, according to the press release, are prone to develop a more severe bout of genital lesions when infected with HSV2. Their findings? The vaccine prevented genital lesions in the guinea pigs. Although they noted that the vaginal swabs did present with a “small amount of viral DNA,” they found that “only a tiny fraction” of it would be able to replicate, according to the press release.

The study’s lead author, Sita Awasthi, PhD, research associate professor of Infectious Diseases at Penn said in the press release, “We are pleased to have demonstrated such a potent and durable immune response to the vaccine. 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."

Dr. Friedman added, “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.” This means that, “in principle,” it would potentially prevent HSV2 from spreading throughout the population. He told Contagion®, "We won't know how good it will be in humans. We hope to test our trivalent vaccine in humans to find out."

Dr. Friedman is currently in the process of discussing with pharmaceutical companies the possibility of taking the promising vaccine to clinical trials.

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