In a study published earlier this year in the Virology Journal, MSU virologist William Halford showed that mice vaccinated with a live, genetically-modified herpes simplex virus type 1 (HSV-1) showed no signs of disease 30 days after being exposed to a particularly lethal "wild-type" strain of the virus.
In contrast, a second group of mice that received a more conventional vaccine died within six days of being exposed to the same "wild-type" strain.
"We have a clear roadmap for producing an effective live vaccine against genital herpes," said Halford, who works in MSU's Department of Veterinary Molecular Biology. "Although my studies were performed with HSV-1, the implications for HSV-2-induced genital herpes are clear. Overall the two viruses are about 99 percent genetically identical."
An estimated 55 million Americans carry herpes simplex virus type 2 (HSV-2), which causes genital herpes. Infection is life-long. Approximately 5 percent of those with genital herpes - 2 million to 3 million Americans - suffer outbreaks one to four times annually. A vaccine offering life-long protection does not exist.
The key to Halford's research was understanding how the herpes simplex virus overcame the body's natural defenses.
A cell infected with the herpes simplex virus sends a warning to neighboring cells. This warning -- an interferon response -- causes neighboring cells to enter "an anti-viral state" akin to putting on a suit of armor, Halford said.
However, herpes produces a protein, ICP0, that tricks every infected cell into destroying its own armor. Once the cell's armor is gone, the virus can propagate itself and spread to other cells, which are in turn tricked into lowering their defenses.
In his research, Halford created a vaccine where the genetic instructions that make ICP0 were disrupted. Without instructions on how to do its clever ICP0 trick, the virus can still establish an infection in animals, but the spread of the virus is stopped long before disease can occur.
"In short, we can disarm the virus such that it is absolutely unable to cause disease, but is still remarkably potent as a vaccine," Halford said.
In a human vaccine, the genetic instructions for ICP0 would actually be removed, creating an "attenuated," or weakened virus. The rest of the herpes simplex virus' genetic code would remain intact. Measles, mumps, rubella, polio and yellow fever vaccines are all made from attenuated viruses.
Research in recent decades has focused on subunit vaccines, which are made from one piece of a virus (a protein subunit). Subunit vaccines are safer than attenuated virus vaccines because the subunit cannot replicate or cause disease. However, subunit vaccines have proven ineffective in protecting people against persistent infections like genital herpes and AIDS, Halford said.
"From a theoretical standpoint, subunit vaccines are poor mimics of a natural virus infection," Halford said. "There's not enough there for our immune systems to build a protective response against the actual virus."
Halford, 38, is aware that his approach is controversial.
"This is where I'm young enough that I don't know how long it can take to swing popular opinion among scientists and clinicians," he said. "I would hope that in five to six years the scientific community would be willing to seriously consider these proposals."
Halford hopes to find a commercial partner or secure government funding to advance his research toward a human vaccine.
"I'd like to take this concept from the chalkboard to the clinics," he said.
Contact: William Halford at (406) 994-6374 or email@example.com, http://vmb.montana.edu/faculty/halford/.
William Halford | EurekAlert!
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