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VCV vaccine vector.?
Mar 23, 2003

VSV Vaccine Vector Provides Long-Term Protection Against Simian AIDS

By Deborah Mitchell

ANNECY, France (Reuters Health) - After vaccination with a recombinant, attenuated vesicular stomatitis virus (VSV) vector expressing Env and Gag proteins of simian-human immunodeficiency virus (SHIV), six out of seven rhesus monkeys have no detectable virus 3 years after SHIV challenge, and none of the animals has developed AIDS.

Human trials of this vaccine approach are currently in the planning stages. These findings were reported here by Dr. John Rose of Yale University in New Haven, Connecticut, at the XIII Cent Gardes meeting attended by international leaders in the field of AIDS vaccine research. The conference was organized by the Foundation Merieux in partnership with Aventis Pasteur and with the participation of the International AIDS Vaccine Initiative.

The study is a continuation of a trial previously reported by Rose et al. (see Reuters Health reports "Vesicular stomatitis virus holds promise as human AIDS vaccine vector," Sept. 7, 2001, and "Modified vesicular stomatitis virus vectors may permit efficient boosting," Dec. 18, 2000).

The vector is made from a "very simple membrane-enveloped rhabdovirus that grows to high titers and causes self-limiting disease," Dr. Rose told the audience.

Building on the previous trial, Dr. Rose and colleagues compared immune responses of animals vaccinated intranasally (IN) or intramuscularly (IM) with the attenuated VSV recombinants. Animals vaccinated via the IN route had much higher cellular immune responses to Env and Gag than did those vaccinated via the IM route. No significant differences in antibody responses between the two groups were seen.

"Clearly the IN route is much better than that IM route," he said. "IN administration was also superior to intravaginal challenge."

VSV vectors expressing HIV env and gag induce a strong cellular immune response, Dr. Rose concluded. "This could be an ideal vaccine for humans."

Although there has been a good deal of pessimism at the conference following disappointing reports from several trials of vaccines designed to induce cytotoxic T lymphocyte responses, the VSV vaccine-induced protection from disease progression for more than 2 years shows that significant progress has been made in the field, Dr. Rose told Reuters Health.

At the moment, Wyeth Vaccines, which collaborated in these investigations, is in the planning stages of a phase I trial using this vaccine vector, Dr. Rose said.

Other conference attendees were impressed by the data. "I was struck by the robust protection that he got in his animal trials," Dr. David Baltimore, of the California Institute of Technology in Pasadena, commented. The strategy is especially attractive because the vector is easily made and easily administered intranasally, he added.

you guys hear anything about this? When does is go into human trials? Sounds pretty amazing to me..

Response from Dr. Young

I'm aware of this particular study, but can't say when or if the product will reach human clinical trials.

I always want to caution about too much enthusiasm for products that are yet to reach even phase I trials-- the likelihood of success is probably less than 1 in 5 to 1 in 10.

Either way, immune-based therapies for HIV are under intense investigation, both for prevention as well as therapeutics for those with established HIV infection. I'm sure that our community will be looking for these results with intense interest. -BY



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