For more than a decade, scientists around the world have worked on designing and testing a safe and effective vaccine to prevent HIV transmission. One such study was the RV144 Thai study, which in 2009 was the first study to show that a vaccine had some level of protection against HIV. A recent study published in Nature Communications builds upon that promise and seeks to create an HIV vaccine that targets multiple strains.
The animal study, led by Duke University scientists, built on the human vaccine design tested in the RV144 trial to develop an investigational vaccine using a combination of five targets in one, known as a pentavalent vaccine. The researchers found that their vaccine regimen increased protection against an HIV-like virus in monkeys significantly more than the RV144 trial in Thailand, where an estimated 440,000 people live with HIV.
Whereas the RV144 trial saw only 31.2% effectiveness, the Duke-led study raised the protection rate to 55.6% -- a 24% difference, though to be clear, while very promising, the 55.6% effectiveness has only been shown in monkeys for now.
"It worked very nicely," Bette Korber, Ph.D., a laboratory fellow at Los Alamos National Laboratory who led the vaccine design told TheBody.com. "We were able to get responses that were able to protect against the challenge quite well."
Researchers added three more targets to the foundation of the RV144 vaccine to create a pentavalent protein boost vaccine regimen, according to the nonhuman primate (NHP) study. In designing the vaccine, Korber said she tried to capture the multiple strains and types of HIV found among the Thai population.
The limitation of the RV144 trial, she said, was that the vaccine that was developed did not account for the different strains of the HIV virus known to the region.
"HIV is an incredibly diverse virus. Every infection is different from every other infection," Korber told TheBody.com. "The immune system is really good at targeting things very intensely, so you will make a really good response to that one vaccine, but that vaccine won't reflect all of the circulating strains very well."
For the animal trial, Korber said she wanted to "get the best coverage you can for a small set" of targets in the vaccine that would protect against an HIV-like virus -- in this case, the simian-human immunodeficiency virus (SHIV). "If you just put in one, you can make a good response, but it's not going to carry over and protect against any other," she said.
Senior study author Barton F. Haynes, M.D., described this vaccine design as the "more-is-better" approach. The researchers collected samples from 110 individuals infected during the RV144 study, including vaccine and placebo recipients. These samples were used as a baseline for the investigational vaccine, which included three additional proteins from the viral envelope -- the outer coat of the HIV virus that is made up of two layers of fatty molecules.
"The RV144 vaccine induced immune responses against one variant of the outer coat protein to protect," said Haynes, director of the Human Vaccine Institute at the Duke University Medical Center. "We have added more variants of the outer coat to improve protection."
The five targets elicited antibody responses fairly easily, Haynes said. Five out of nine primates given the pentavalent vaccine remained uninfected, improving the level of protection against a difficult-to-neutralize strain of SHIV.
"That's a pretty strong indicator" that their investigational vaccine could translate to humans, Haynes said.
The research team received the Center for HIV/AIDS Vaccine Immunology-Immunogen Discovery grant from the NIH's National Institute of Allergy and Infectious Diseases and a Collaboration for AIDS Vaccine Discovery grant from the Bill & Melinda Gates Foundation.
Haynes said that, as a next step, the team plans to perform a similar macaque monkey study with a pentavalent vaccine designed for HIV strains found in Africa. Korber added that the researchers might also work on a vaccine for HIV viruses in North America and Europe. Those animal studies should take another one or two years of work, she said.
"We're going to keep doing these parallel studies to try to explore other regional vaccines," Korber told TheBody.com.
She said she would also look into reducing the number of vaccine proteins to see whether a smaller set would have as good of a response as the one tested for the Nature Communications study.
Overall, Korber said the immunology field is advancing in designing and testing vaccines to prevent HIV transmission. Scientists are working on many "new, beautiful ideas," although that research is in the early stages, she noted. Still, Korber said that she hopes at least one of those experiments will be able to "move forward within a reasonable timeframe" so that a safe, effective and affordable HIV vaccine becomes available.
"For HIV, it's really challenging to get one, but once we have one, it would be fantastic because it's the kind of thing you don't have to take your [whole] life," Korber told TheBody.com. "That's why we keep trying."