Microbicide and Vaccine, Sidekicks at Last?

Results from an initial study combining a microbicide candidate and experimental vaccine are promising enough to at least keep Imperial College virologist Robin Shattock coming back for more in pursuing what could be a novel move in preventing HIV infection.

Shattock collaborated with French immunovirologist Roger Le Grand and colleagues to evaluate a microbicide alone, a vaccine alone, or the two in combination in three groups of rhesus macaques, all of which were compared to a group of control monkeys that received no intervention.

Shattock and colleagues intentionally used less than full-strength elements in the experiment in order to better measure their effects when brought together. “We needed to have a vaccine and a microbicide that were not fully protective. We went for a microbicide strategy that we hoped would give us a low level of protection in order to see if there was any benefit to combining it with the vaccine,” Shattock says.

The vaccine candidate consisted of two HIV gp140 uncleaved trimers, provided by pharmaceutical company Novartis, which were administered nasally in three doses to the monkeys with R848 as an adjuvant, followed by two booster injections of MF59—an adjuvant developed by Novartis and used to improve immune response to its influenza vaccine. For the microbicide, Le Grand and Shattock’s team used a one percent tenolfovir gel solution.

Results? The group was able to characterize the antibodies made by the animals following a hybrid simian/human virus known as SHIV. “We got very good neutralizing titers,” Shattock says, referring to the levels of neutralizing antibodies induced by the combination of the vaccine and microbicide candidates. Researchers observed no protection from the vaccine candidate alone; however, the microbicide alone reduced infection rates by 46 percent in the animals after six low-dose, intra-vaginal SHIV challenges.

The combination of the vaccine and microbicide fared even better, with that group of monkeys boasting an 81% reduced rate of SHIV infection, compared to the untreated animals. It’s early days yet, Shattock says—the full results of the experiment should be published in the next few weeks—but the group likes where the research is headed and think it is worthwhile pursuing. “It may be a good thing. There’s no evidence of it being a bad thing,” Shattock says.

This combination approach is also receiving support from HIV elder statesman Anthony Fauci, director of the US National Institute of Allergy and Infectious Diseases, who addressed delegates yesterday by video link as he remained stateside to respond to the Ebola outbreak. In his address, he exhorted researchers to bring non-vaccine prevention and vaccine research efforts together. “If we do both, and do it with intensity, we will be successful in ultimately ending the HIV/AIDS pandemic.” – Michael Dumiak