In a significant find, a team of researchers has reported for the first time elicitation of powerful, HIV-blocking antibodies in cows in a matter of weeks — a process that usually takes years in humans — paving the way for developing a broadly effective AIDS vaccine in the near future. According to the study, published in the prestigious journal Nature, the unexpected discovery in cows is providing clues for important questions at a moment when new energy has infused HIV vaccine research.
“One approach to a preventive HIV vaccine involves trying to elicit broadly neutralising antibodies in healthy people, but so far the experiments have been unsuccessful, in both human and animal studies,” said lead author Devin Sok, Director, Antibody Discovery and Development at the International AIDS Vaccine Initiative (IAVI).
“This experiment demonstrates that not only is it possible to produce these antibodies in animals, but we can do so reliably, quickly, and using a relatively simple immunisation strategy when given in the right setting,” Sok added.
Scientists have known that some people living with chronic HIV infection produce broadly neutralising antibodies (bnAbs), which can overcome the high levels of diversity of HIV. One type of bnAb uses long, arm-like loops that are capable of reaching concealed areas on the virus’s surface to block infection. The scientists had a question: what would happen if they immunise cows with an HIV immunogen? “The answer began with a single protein on HIV’s surface that serves as a bnAb target — develop an antibody that recognises variants of this protein on different HIV viruses and you’ll likely be protected from all of them,” the study said.
One of the many tricks that HIV uses to prevent humans from developing the right antibodies is to display irrelevant forms of this protein to distract the immune system. Scientists thought they had overcome this challenge by developing an immunogen called “BG505 SOSIP”, which closely mimics the protein target. In the new study, four cows immunised with “BG505 SOSIP” elicited “bnAbs” to HIV within 35-52 days.
In comparison, it takes HIV-positive humans multiple years to develop comparable responses, and only 5-15 per cent even develop them at all. “Cows cannot be infected with HIV, of course. But these findings illuminate a new goal for HIV vaccine researchers: by increasing the number of human antibodies with long loops, we might have an easier chance of eliciting protective bnAbs by vaccination,” the researchers noted.
There is no doubt that cows’ ability to produce bNAbs against a complicated pathogen like HIV in a matter of weeks, highlights even broader significance, particularly for emerging pathogens.
Sok is an affiliate of IAVI’s Neutralising Antibody Center (NAC), a part of The Scripps Research Institute (TSRI) where multiple groups of scientists work collectively on an antibody-based HIV vaccine.