Cows yield important clues for human vaccine research

Animal model provides clues for answering important questions in human vaccine research.

Cows are leaving the pasture and contributing to the field of HIV vaccine research.

As outlined in a recent study published in Nature, lead author Devin Sok, director of antibody discovery and development at the International AIDS Vaccine Initiative (IAVI), reported the elicitation of powerful, HIV-blocking antibodies in cows in a matter of weeks — a process that usually takes years to occur in humans.

The animal model is providing clues for answering important questions at a moment when new energy has been infused into HIV vaccine research.

"One approach to a preventive HIV vaccine involves trying to elicit broadly neutralizing antibodies (bnAbs) in healthy people, but so far, the experiments have been unsuccessful in both human and animal studies," Sok said. "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 immunization strategy when given in the right setting."

Scientists have known for some time that some people living with chronic HIV infection produce bnAbs, which can overcome the high levels of diversity of HIV. One type of bnAb — first reported in Science in 2009 by IAVI, The Scripps Research Institute (TSRI) and Theraclone — uses long, arm-like loops that are capable of reaching concealed areas on the virus's surface to block infection.

Previous experiments led by bovine antibody expert Vaughn Smider at TSRI showed that cattle antibodies also feature extra-long loops, which researchers thought might access difficult epitopes that human antibodies cannot.

For the study, an alliance of HIV, antibody and veterinary medicine scientists from IAVI, TSRI and Texas A&M University posed the question: What would happen if we immunized cows with an HIV immunogen?

"It's a remarkably simple and profound idea," Sok said. "Since we know that some human bnAbs have longer-than-average loops, would immunizing animals with similar antibody structure result in the elicitation of bnAbs against HIV?"

One of the many tricks HIV uses to prevent people 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.

All four cows immunized with BG505 SOSIP elicited bnAbs to HIV within 35-52 days. In comparison, it takes HIV-positive people multiple years to develop comparable responses, and only 5-15% develop them at all.

Cows cannot be infected with HIV, but these findings illuminate a new goal for HIV vaccine researchers: By increasing the number of human antibodies with long loops, it might help the chance of eliciting protective bnAbs by vaccination.

There is no doubt that cows' ability to produce bnAbs against a complicated pathogen like HIV in a matter of weeks has even broader significance, particularly for emerging pathogens.

"Scientific innovations like this are what propel the field forward," IAVI chief executive officer Mark Feinberg said. "This surprising set of results warrants further exploration and has potential applications not only to HIV prevention and treatment but to the rapid development of antibodies and vaccines against other infectious diseases."

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