HIV Vaccine in Monkeys Suggests Human Vaccine on the Horizon

So far, a vaccine for HIV has been elusive. However, researchers with The Scripps Research Institute recently published positive data about its HIV vaccine in the journal Immunity that suggests one might be on the horizon.

A long way from human trials, the vaccine in rhesus macaque monkeys produced neutralizing antibodies against one strain of HIV that is similar to the most common strain. It also resulted in the first-ever estimate of what antibody levels would be needed to protect against HIV.

“We found that neutralizing antibodies that have been induced by vaccination can protect animals against viruses that look a lot like real-world HIV,” stated Dennis Burton, chair of Scripps Research’s Department of Immunology and Microbiology, and scientific director of the International AIDS Vaccine Initiative (AIVI) Neutralizing Antibody Center.

The trial offers proof-of-concept for Burton’s HIV vaccine strategy, which he and his colleagues have been working on since the 1990s. The strategy is to identify the vulnerable areas on HIV and then stimulate the immune system’s antibodies to attack those rare areas.

Research so far has indicated that the body must produce neutralizing antibodies that bind to the HIV’s outer envelope protein trimer. Burton and his team determined they could protect animals from HIV by injecting them with neutralizing antibodies produced in the lab.

They then needed to get the animals’ immune systems to make the neutralizing antibodies themselves. The researched exposed the animal immune systems to the envelope protein trimer, which basically trained their immune systems on how to identify, target and create the appropriate antibodies.

The key challenge was that the HIV envelope trimer is unstable and disintegrates when isolated. But in 2013, they genetically engineered a more stable trimer called SOSIP.

“For the first time, we had something that looked pretty much like the HIV envelope protein trimer,” stated Matthias Pauthner, a research associate at Scripps and co-first author of the study.

The new experimental vaccine contained the stable SOSIP trimer, which they tested in two groups of rhesus monkeys. Previous studies had shown that immunized monkeys naturally developed low neutralizing antibody levels, while others developed higher levels. So the team chose and re-vaccinated six monkeys who had previous low levels and six that previously had high levels. They had another 12 unimmunized monkeys as the control group.

The monkeys were then exposed to a strain of the virus called SHIV, an engineered simian version of HIV that has the same envelope trimer that’s found in the human virus.

The results were the vaccine worked in the animals with the high levels of antibodies. The animals produced high enough levels of neutralizing antibodies against the envelope protein trimer to prevent infection.

The researchers are working to develop broadly neutralizing antibodies (bnAbs) that can neutralize more strains of HIV instead of just the single strain used in the study.

Although the research marks significant work in identifying the neutralizing antibodies as vital in long-term immune protection, much more research needs to be done before the vaccine could be tested in humans and proof of long-term efficacy and safety is evaluated. “There are many immunological tricks that can be explored to make immunity last longer,” Pauthner stated.