New approach offers hope for an effective herpes vaccine

Jan 10 2007

A researcher at Montana State University has called for an innovative, new approach in developing a vaccine against genital herpes.

In an editorial published in the January issue of Future Virology, virologist William Halford has proposed that genetic engineering of live strains of herpes simplex virus (HSV) can be used to obtain safe and effective vaccines that confer life-long immunity against genital herpes and other diseases caused by HSV.

Approximately 4 billion people worldwide are infected with herpes simplex virus types 1 and 2 (HSV-1 and HSV-2). Infection is life-long. The majority of carriers experience no symptoms (80%), but infection with HSV-1 or HSV-2 cause diseases including genital and oral herpes in the remainder of infected persons.

Amongst those who do exhibit symptoms, approximately 2-5% suffer recurring outbreaks one to four times annually and it is estimated that 50 million people worldwide suffer from recurrent genital herpes disease.

HSV-1 and HSV-2 can also produce lethal or seriously debilitating infections in newborn babies (neonatal herpes) or adults (herpes encephalitis). Although considered rare, the 5000 deaths that occur worldwide per year due to complications of HSV infections dwarfs the combined annual incidence of bird flu, Ebola virus, SARS and anthrax.

Numerous vaccine candidates have been proposed over the past 30 years, but none of these have proven to be effective. Thus, the medical community is still helpless to prevent the ongoing genital herpes epidemic.

Most vaccine research has centred on developing viral protein subunits or replication-defective viruses that can be used to vaccinate against genital herpes. In both cases, the vaccine is transient in nature, and is cleared from the body within days to weeks.

Dr. Halford disagrees with this approach; "These approaches are touted as "safe" because the vaccine does not permanently establish itself in the body. However, life-long HSV infections may be a prerequisite for acquiring and maintaining effective immunity to herpetic diseases. If correct, a live HSV virus is the only approach that can be used to achieve the desired goal. After 30 years of failed herpes vaccine candidates, perhaps it is time that we consider a new approach. Genetically engineered, live HSV strains that persist in the body could be used to vaccinate against genital herpes. As obvious as this approach is, we have simply never explored it because of safety concerns."

Dr. Halford believes that an effective herpes vaccine can be developed by mimicking the asymptomatic carrier state that currently exists in 3 billion people worldwide. Such persons carry ‘wild-type' strains of HSV-1 and/or HSV-2 for life, maintain high levels of antibodies against the virus, but never experience any disease.

Dr Halford's other recent studies published last year in the Virology Journal, have shown that mice vaccinated with a live HSV-1 virus that lacks the viral ICP0 gene were effectively immunized when exposed to a particularly lethal ‘wild-type' strain of HSV-1.

In the past, safety concerns have limited consideration of live HSV vaccines but Dr Halford believes that this should not stand in the way of exploring this new approach. He states; "In erring on the side of caution, perhaps we have overlooked the most feasible approach to vaccinating against genital herpes……live, attenuated HSV vaccines."

Dr. Halford adds; "Surely we are well placed to explore this exciting possibility regarding the use of live viruses to vaccinate against HSV-1 and HSV-2. However, I wonder if this is indicative of a bigger story. My ICP0- strains of HSV lack a single viral countermeasure to the innate immune response of the host."

He continues; "If an effective herpes vaccine can be obtained by simply removing one key gene from a virus, perhaps this strategy has parallels in other persistent infections. Perhaps excision of immune evasion factors may be applied to attenuate other persistent infectious agents. If correct, live, attenuated strains of other infectious agents could be manufactured for the purpose of vaccinating against AIDS, viral hepatitis, or tuberculosis."

He concludes; "Of course, my focus lies in developing an effective vaccine against genital herpes. However, the excision of immune-evasion genes represents a completely unexplored approach to developing vaccines against persistent infectious agents."

http://www.future-drugs.com and http://www.futuremedicine.com