Global Health Press
Unconventional design approach shows promise for new herpes vaccine

Unconventional design approach shows promise for new herpes vaccine

herpesHerpes is one of the most common sexually transmitted diseases, affecting close to 500 million people worldwide, yet an effective vaccine against the pernicious virus has eluded scientists for decades.

However, Howard Hughes Medical Institute (HHMI) researchers at Albert Einstein College of Medicine have now designed a new vaccine that was able to prevent both the active and latent infection stages of herpes simplex virus type 2 (HSV-2).

“Developing a herpes vaccine is one of the holy grails of infectious disease research,” said William Jacobs Jr., Ph.D., HHMI investigator at Einstein and co-senior author on the study. “We decided to take an approach that runs counter to most of the tactics used by other scientists—and we seem to have cracked the code.”

Traditional approaches to HSV-2 vaccine design went with the assumption that the vaccine must stimulate the body to produce neutralizing antibodies, especially against the viral surface protein called glycoprotein D (gD-2), which HSV-2 uses to enter the host cell. Unfortunately, this methodology has not yielded a vaccine that has been able to prevent herpes infections within humans.

“This suggests we’ve been stimulating production of the wrong type of antibodies,” stated co-senior author Betsy Herold, M.D., Harold and Muriel Block Chair in pediatrics at Einstein.

The Einstein team was determined to take a different approach when designing their live HSV-2 vaccine. They decided to delete gD-2 from the virus’ genome. This had the effect of incapacitating the virus, making it unable to infect cells or cause disease. The researchers also hypothesized that the gD-2 deletion would stimulate the host immune system to produce different and more efficacious antibodies.

“We had a hunch that gD-2 might be masking other viral antigens, and that by removing this dominant protein we would expose those previously masked antigens to the immune system,” explained Dr. Jacobs.

Dr. Jacobs and his colleagues found that mice immunized with their newly generated vaccine provided complete protection from subsequent challenges with wild-type HSV-2, either intravaginally or through the skin. Furthermore, the researchers were unable to detect any latent HSV-2 virus at the challenge site in the immunized mice.

“Our findings challenge the existing dogma that says an effective herpes vaccine must stimulate neutralizing antibodies against gD-2,” said Dr. Jacobs. “It’s almost as if the virus evolved gD-2 specifically to hide the other antigens. gD-2 turns out to be a Trojan horse that misleads the immune system.”

The results from this study will be released on March 10 online in eLife through an article entitled “Herpes simplex type 2 virus deleted in glycoprotein D protects against vaginal, skin and neural disease”.

Because vaccine safety is a prevailing concern to public health, the Einstein team calculated the amount of wild-type virus that would be required to kill a mouse and then challenged mice lacking an immune system with the vaccine at 1,000 times the calculated lethal wild-type dose. Not only did the mice survive, none of them developed any signs of herpes.

The Einstein researchers are hopeful that their novel design will spawn new vaccine development for other viral infections where an effective vaccine is desperately needed.

“Genital herpes infections can not only be serious in and of themselves, but they also play a major role in fueling the HIV epidemic,” explained Dr. Herold. “People infected with HSV-2 are more likely to acquire and to transmit HIV—which further underscores the need to develop a safe and effective herpes vaccine.”

Source: GEN – Genetic Engineering & Biotechnology News