timberland shearling jacket Experimental herpes vaccine upends traditional approach and shows promise
March 10, 2015 (BRONX, NY) Scientists at Albert Einstein College of Medicine of Yeshiva University have designed a new type of vaccine that could be the first ever for preventing genital herpes one of the most common sexually transmitted diseases, affecting some 500 million people worldwide. By using a counterintuitive scientific approach, researchers were able to prevent both active and latent infections caused by herpes simplex virus type 2 (HSV 2), the virus that causes genital herpes. Findings from the research, conducted in mice, were published today in the online journal eLife. “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.” Dr. Jacobs is also professor of microbiology immunology and of genetics at Einstein.
It was generally assumed that an effective HSV 2 vaccine must stimulate the body to produce neutralizing antibodies particularly against a viral surface protein called glycoprotein D (gD 2) that HSV 2 uses to enter human cells. A protein that triggers antibody production is called an antigen. For decades, researchers have focused on “subunit” herpes vaccines that rely primarily on gD 2 as the antigen to stimulate the body’s antibody response but none has prevented HSV 2 infection in humans. Dr. Herold is also professor of pediatrics, of microbiology immunology, and of obstetrics gynecology and women’s health at Einstein.
The Einstein team took a completely different approach in designing their “live” HSV 2 vaccine. Instead of using gD 2 to stimulate antibodies, they deleted the gene for gD 2 from the virus (and, consequently, the protein’s expression on the viral surface) a manipulation that weakens the virus, rendering it unable to infect cells or cause disease. They hypothesized that this altered virus would stimulate the body to produce different and more effective 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,” said Dr. Jacobs.
When the vaccine, dubbed “delta gD 2” (“delta” is shorthand for a gene deletion) was given to mice, it provided complete protection against subsequent infection with normal (wildtype) HSV 2, whether animals were challenged intravaginally or through the skin. No virus was detected in vaginal or skin tissue of vaccinated mice or in neural tissue, where HSV 2 often hides in a latent form only to emerge later to cause disease. When unvaccinated mice were challenged with wildtype HSV 2, all showed evidence of the virus in the three tissue sites, and all succumbed to the disease.
The vaccinated mice showed low levels of neutralizing antibodies but high levels of antibodies associated with a different immune response called antibody dependent cell mediated cytotoxicity (ADCC). This and other experiments described in the paper such as finding that blood serum from vaccinated mice was able to passively protect unvaccinated mice conclusively demonstrated that ADCC antibodies were responsible for protecting against HSV 2.
“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 new vaccine also appears to be safe. The researchers calculated the number of wildtype viruses needed to kill mice and then administered 1,000 times that number of delta g D 2 viruses to mice that lacked immune systems and so couldn’t ward off infections. The result: The mice survived and didn’t develop herpes. The Einstein team hopes to begin clinical trials on humans within a few years.
Initial tests suggest that the vaccine is also effective against HSV 1, or oral herpes, although this needs to be further evaluated. In addition, the vaccine’s novel design may help in creating vaccines against other disease causing microbes that invade the body through mucosal tissues,
including HIV and the bacterium that causes tuberculosis.
“Genital herpes infections can not only be serious in and of themselves, but they also play a major role in fueling the HIV epidemic,” said 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.”
Albert Einstein College of Medicine has filed patent applications related to this research and is seeking licensing partners able to further develop and commercialize this technology.
The study was support by grants from the National Institute for Allergy and Infectious Diseases, part of the National Institutes of Health (AI065309, AI03461, AI084225 and AI063537) and the Howard Hughes Medical Institute.
There are two types of herpes simplex virus: HSV 1 (more commonly associated with oral herpes) and HSV 2 (more commonly associated with genital herpes). Neither genital herpes nor oral herpes can be cured.
Oral herpes typically causes sores around the mouth and lips and is transmitted through oral secretions or skin sores. Oral herpes is a leading cause of corneal blindness worldwide.
Most people with genital herpes are symptom free but periodically shed the virus, which they may unknowingly transmit to their partner or newborn. Genital herpes sores typically appear as one or more blisters on or around the genitals, rectum, or mouth. The blisters break and leave painful sores that may take weeks to heal. The first of these “outbreaks” may be accompanied by flu like symptoms. Repeat outbreaks are common, especially the first year after infection. Although genital herpes infection can persist for life, the number of outbreaks tends to decrease over time. program, and 313 . The College of Medicine has more than 2,000 full time faculty members located on the main campus and at its clinical affiliates. In 2013, Einstein received more than $150 million in awards from the National Institutes of Health (NIH). This includes the funding of major research centers at Einstein in aging, intellectual development disorders, diabetes, cancer, clinical and translational research, liver disease, and AIDS. Other areas where the College of Medicine is concentrating its efforts include developmental brain research, neuroscience, cardiac disease, and initiatives to reduce and eliminate ethnic and racial health disparities. Its partnership with Montefiore Medical Center, the University Hospital and academic medical center for Einstein, advances clinical and translational research to accelerate the pace at which new discoveries become the treatments and therapies that benefit patients. Through its extensive affiliation network involving Montefiore, Jacobi Medical Center Einstein’s founding hospital, and three other hospital systems in the Bronx, Brooklyn and on Long Island,
Einstein runs one of the largest residency and fellowship training programs in the medical and dental professions in the United States.