The Search for a Vaccine: NIAID Researcher seeks effective Vaccine against Genital Herpes
The search for a herpes cure has always been a public health priority. It has taken on new urgency with the recent discovery that people infected with herpes simplex virus type 2 (HSV-2), the leading cause of genital herpes, are more likely to become infected with HIV and transmit it to others. If scientists can create a vaccine to reduce the spread of genital herpes, they may be able to help curb HIV transmission as well.
Jeffrey Cohen, M.D., chief of the Medical Virology Section in the NIAID Laboratory of Clinical Infectious Diseases, is focusing his efforts on a new herpes vaccine candidate called dl5-29. Dr. Cohen is currently testing the vaccine, which was developed by Harvard researcher David Knipe, Ph.D., to see if it will prove more effective for broader populations than other candidate vaccines.
The Struggle Against Herpes
According to the Centers for Disease Control and Prevention (CDC), at least 45 million people ages 12 and older in the United States, or one in five adolescents and adults, have had genital herpes. Most people with the disease are unaware that they have it. Some develop painful symptoms, such as recurring sores around the genitals or rectum. The virus is transmitted almost exclusively through sexual contact, though pregnant women with herpes outbreaks can also infect their babies during delivery.
Herpesviruses have proven difficult for the human immune system to control. All eight herpesviruses that infect humans, including HSV-2, can go dormant and will survive in the body for life. While dormant, herpesviruses produce few, if any, viral proteins for the immune system to detect and combat. HSV-2 also eludes the immune system by hiding out in neurons, where antibodies can’t attack it effectively. In addition, HSV-2 interferes with the activity of antibodies, T cells, and other major components of the immune system.
The Search for a Vaccine
Herpesviruses are tough to beat. However, the success of vaccines for chickenpox and shingles, which are caused by a herpesvirus called varicella-zoster virus, suggests that vaccines may work for HSV-2. First, scientists must determine what kind of vaccine will be most effective against HSV-2.
With a live, attenuated vaccine, like the one for chickenpox, a weakened version of a virus is injected into a person’s body to stimulate an immune response. So far, scientists do not know which genes they would need to remove from HSV-2 to ensure that a live, attenuated herpes vaccine would stimulate an immune response without causing disease.
Some researchers have tried a different approach with Herpevac, a candidate vaccine with just one glycoprotein, or carbohydrate-protein molecule, from the virus. Herpevac is now in clinical trials co-sponsored by NIAID and GlaxoSmithKline and has shown some promise. However, its effectiveness seems limited only to women who test negative for both HSV-2 and HSV-1, the common cause of cold sores. The vaccine has not benefited men, regardless of HSV diagnosis.
Dr. Cohen is working to understand why other vaccine candidates have not been fully effective against HSV-2 by comparing them in laboratory tests against the dl5-29 vaccine virus. This vaccine has more than 80 proteins of HSV-2 but is replication-defective, meaning that the virus in it cannot grow or make copies of itself in animals or people. In early tests with mice and guinea pigs, the vaccine has stimulated a strong immune response, and Dr. Cohen hopes to extend testing to humans in the future.
Meanwhile, he is undertaking other studies to learn more about how herpesviruses become dormant in the body and to measure how much virus is present in infected nerve tissue. His findings may have potential benefits for vaccine development and ultimately give scientists better insight into the human immune system.
For more information, visit NIAID’s Web site on genital herpes or the CDC’s genital herpes fact sheet.
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