Dr. Stanberry summarized the current status of HSV-2 vaccine development at the 44th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) here.
Therapeutic vaccines, by contrast, are designed to eliminate chronic infection, or, if that is not possible, then to reduce the frequency or severity of disease outbreaks in individuals who are already infected, Dr. Stanberry tells Dermatology Times.
"Herpes is a notoriously unreliable partner in the development of stable attenuation," Dr. Stanberry says. "You can get attenuation, and then for unpredictable reasons, the virus will revert to wild-type. So that strategy has been abandoned."
Live, genetically attenuated vaccines take the tissue culture strategy one step further by selectively removing genes important in virulence or latency. This strategy appears to hold promise, but to date has not been successful.
A variation on the strategy is to develop a vaccine using replication-impaired virus, in which one or more genes essential for viral replication inside the host cell have been removed by genetic engineering. In this strategy, the cell line used to grow the virus has been engineered to express the necessary genes and produce the missing proteins, although normally the viral genes would not be present in the host cells.
"The virus is grown in a complementing cell line so that the viral progeny that come out have the missing gene products and, therefore, are capable of causing infection, but because the progeny lack the gene that produces the missing protein, the virus can only go through a single round of replication before it shuts down," Dr. Stanberry explains.
Viral subunits (purified proteins), rather than the entire virus, can constitute a vaccine. Also, nucleic acid-based vaccines, such as DNA vaccines, have been actively studied, but there has been a problem with the "primate barrier."
"Nucleic acid-based vaccines work wonderfully in small animals, but not in non-human primates or humans," Dr. Stanberry says. In another promising approach, vectored or chaperoned vaccines use an unrelated protein or microbe to deliver the epitope to the antigen-presenting cells.
Two large phase 3 studies in discordant heterosexual couples, enrolling over 3,000 volunteers, have been completed. The vaccine afforded significant protection against HSV disease in seronegative women but had no effect whatsoever in HSV-1 seropositive women or men of any serological status.
"What was very exciting about it was that it was the first study done that demonstrated the feasibility of a vaccine to control herpes disease," Dr. Stanberry says.