“We think this is both a theoretical advance as well as a practical one,” said Dan A. Barouch of Harvard Medical School, who led the research.
“As far as animal trials go, this is a solid step in trying to track down the [biological markers] of immunity,” said Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases at the National Institutes of Health, which provided partial funding of the study.
A two-vaccine combination tested in Thailand three years ago protected people against HIV infection about 30 percent of the time — a hopeful, although not useful, outcome. More recently, researchers have been looking for ways to engineer the production of rare protective antibodies that some people make after exposure to HIV. The new research points to another candidate vaccine and sheds some light on how a successful one might work.
Barouch and his collaborators at 10 institutions tried out four real and one sham vaccine on rhesus monkeys. The vaccines used modified cold or herpes viruses to either carry the immunogens or boost the immune response, and sometimes for both purposes.
Previous vaccine studies in monkeys used weak versions of the simian immunodeficiency virus (SIV) that were identical to the components of the vaccine being tested — an arrangement that stacks the deck in favor of the vaccine. These researchers exposed the animals to a highly virulent strain somewhat different from the vaccine, which is a more real-world test.
The best-performing vaccine — which used two different strains of adenovirus that normally causes colds — reduced an animal’s chance of becoming infected by 80 percent (although with enough exposure, infection was inevitable).
Furthermore, once a vaccinated monkey became infected, there was less virus replicating and circulating in the bloodstream than was the case in unvaccinated animals. That is evidence of a more robust immune response fighting the infection.
“This type of protection, and the extent of protection, in non-human primates has not been previously seen,” Barouch said.
When a piece of the SIV’s envelope, or outer shell, was removed from the vaccine, the animals had no protection — confirming previous suggestions that envelope proteins will be an essential component of any AIDS vaccine likely to work.
The researchers also tested the animals that were best able to suppress the growth of SIV after infection. They identified nine components of the immune response (of about 35 measured) that correlated with control of the virus — information that will also be useful in future studies.
The study was partially funded by the Ragon Institute, a Boston charity that has committed $10 million to further testing of the vaccine, Barouch said.