FOR more than 20 years, scientists at Scripps Research have chipped away at the challenges of designing an HIV vaccine. Now new research, published in Immunity, shows that their experimental vaccine strategy works in non-human primates.
The new study shows that rhesus macaque monkeys can be prompted to produce neutralising antibodies against one strain of HIV that resembles the resilient viral form that most commonly infects people, called a Tier 2 virus.
The research also provides the first-ever estimate of vaccine-induced neutralising antibody levels needed to protect against HIV.
“We found that neutralising antibodies that have been induced by vaccination can protect animals against viruses that look a lot like real-world HIV,” says Dennis Burton, PhD, chair of Scripps Research’s Department of Immunology and Microbiology, and scientific director of the International AIDS Vaccine Initiative (IAVI) Neutralising Antibody Center and of the National Institutes of Health’s Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID).
Although the vaccine is far from human clinical trials, the study provides proof-of-concept for the HIV vaccine strategy Burton and his colleagues have been developing since the 1990s.
The goal of this strategy is to identify the rare, vulnerable areas on HIV and teach the immune system to make antibodies to attack those areas.
Studies led by Scripps Research scientists have shown that the body needs to produce neutralising antibodies that bind to the virus’s outer envelope protein trimer. To support this idea, scientists found that they could protect animal models from HIV by injecting them with neutralising antibodies that were produced in the lab.
The challenge then was to get animals to make the neutralising antibodies themselves. To do this, scientists needed to expose the immune system to the envelope protein trimer, effectively training it how to spot this target and produce the right antibodies against it.
But there was a big problem. The HIV envelope trimer is unstable and tends to fall apart when isolated. How could scientists use it as an ingredient in a vaccine? A breakthrough came in 2013, when scientists genetically engineered a more stable trimer, or SOSIP.
“For the first time, we had something that looked pretty much like the HIV envelope protein trimer,” says Matthias Pauthner, PhD, a research associate at Scripps Research and co-first author of the new study.