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Merck's Gardasil offers cross-protection against up to 10 additional types of HPV not represented in the vaccine. Varying degrees of protection may be related to antibodies, memory B cells. Niche-filling is unlikely to occur with HPV, due to its very stable genome.
"In vitro cross-neutralization studies had offered some suggestion that antibodies to closely related types may be able to cross-neutralize other types," says lead investigator Darron Brown, M.D. "But I think that we all are pleasantly surprised with the high degree of cross-protection that was shown to occur, both in terms of resisting infection and, more importantly, disease."
The quadrivalent vaccine protected against approximately 99 percent of persistent infections and almost 100 percent against the development of lesions by those four strains. HPV types 6 and 11 cause about 90 percent of genital warts, while HPV types 16 and 18 account for about 70 percent of all cervical cancers. The cross-protection comes in addition to that.
He suspects that the different degrees of cross-protection the researchers observed are probably related to the level of antibody generated, and perhaps to memory B cells, both of which are likely have an individual genetic component.
All of the data to date have come from studies in women, and there is some reason to be cautious about automatically extrapolating its application to men. He pointed out that there are differences between the cervical and penile epithelium, and in the lesions seen in each tissue.
"However, penile and vulvar epithelium are quite similar. In our studies, vulvar lesions were nearly 100 percent prevented, giving us hope that the vaccine will offer similar cross-protection in analogous penile epithelium. But that data is still being analyzed," he cautions.
Some have hypothesized that preventing infection from these dominant strains of HPV might open up an ecological niche for other strains to expand. Dr. Brown expresses skepticism: "When one looks at situations where there has been replacement or niche filling, these have been pathogens in which mutation is frequent and likely to occur, for example, streptococcus," he says. "In contrast, HPV has a very stable genome and replicates at about the same rate as the human genome.
"Secondly, we would expect that if fill-in would occur, we might see competition between HPV virus types. But we see just the opposite; we see cooperation. If you are infected with 16, you are more likely to be infected with additional oncogenic types."
Dr. Brown says it would be five to 10 years before researchers get a solid sense as to which of the opposing theories of niche-filling could be documented through epidemiologic studies.
John Schiller, Ph.D., conducted some of the initial research into HPV that made the vaccine possible. The senior investigator at the National Cancer Institute, part of National Institutes of Heath (NIH), was not surprised by the data. He says none of the researchers involved with the vaccine trials wanted to build up expectations about possible cross-protection, so they downplayed that aspect of it.