Broadly Neutralizing Antibodies From Cows May Hold the Key to an HIV Vaccine

Devin Sok, Ph.D. (Credit ©IAS/Steve Forrest/Workers' Photos)

It seems that cows may hold the key to developing an HIV vaccine.

In the early 1990s, scientists discovered broadly neutralizing antibodies, known as bNAbs, which are naturally occurring proteins that can protect a cell against a variety of HIV types. Although labs tests have shown that bNAbs can stop most HIV strains from infecting human cells, researchers have failed to elicit production of these powerful antibodies through immunization in human or animal studies -- until now.

According to a new paper published in the journal Nature, cows injected with proteins mimicking HIV were able to rapidly produce bNAbs in their blood as soon as 35 days after immunization. The scientists behind the study consider this a breakthrough in HIV prevention research because "this is the first time we are seeing such strong responses following vaccination," lead author Devin Sok, Ph.D., director of Antibody Discovery and Development at the International AIDS Vaccine Initiative (IAVI), told

Researchers were "very surprised" by their discovery, Sok added. "We have been doing immunization experiments in different animal models for years. For this to work so well, quickly and reliably was above and beyond what we expected."

Most humans do not make broadly neutralizing antibodies. In fact, only about 10% to 20% of people living with HIV can produce bNAbs, and even then only a couple years after being infected with the virus, according to the National Institutes of Health (NIH).

Part of why these antibodies are effective is because of a long loop of amino acids, known as HCDR3, that protrudes from their surface and blocks the viral infection. Humans produce 30 amino acids in that bNAb stretch; bovines, on the other hand, naturally produce longer HCDR3s -- up to 70 amino acids in length, according to the study. The unique nature of antibodies in cows led scientists to test the effects of HIV vaccination in cattle.

According to the study, all the immunized cows rapidly produced antibodies against different HIV strains. The researchers then tested against a 117-virus panel in a serum from one cow; this resulted in 20% neutralization at day 42 and 96% neutralization at day 381. They also identified a particularly potent antibody defending against the virus: NC-Cow 1.

These results have extraordinary meaning for the future of HIV vaccine development, Sok said.

"It means that we now have an answer to the question: If we have long loops to begin with, will we get broadly neutralizing antibodies following immunization with an immunogen that looks like the target protein on the virus?" Sok told "The answer was a resounding yes."

"This suggests that if we can enrich for long loops in humans to start with, then we will have a much easier time to elicit broadly neutralizing antibodies by vaccination," he added.

Researchers first published the Nature study online on July 20; then, Sok presented their findings at the 9th Annual International AIDS Society Conference on HIV Science in Paris.

The research was conducted by an alliance among scientists from the IAVI, the Scripps Research Institute and Texas A&M University. They were supported by the NIH's National Institute of Allergy and Infectious Diseases.

But, despite the study's important findings, Sok acknowledges that research limitations remain. "Cows are not humans, and their immune system is inherently different from ours," he told "Although we have more clarity on what challenges to focus on, those challenges are still challenges."

One major challenge is that cows cannot be infected with HIV. The research was therefore based on an HIV immunogen, which is a protein designed to imitate a key component of the virus.

Nevertheless, this breakthrough discovery has significant implications for the future of HIV prevention and treatment research. In particular, Sok said, the rapid production of broadly neutralizing antibodies gives scientists insight into immune responses, and that may translate into experimental HIV vaccine designs.

"This was the first time we could reliably show the elicitation of broadly neutralizing antibodies to HIV by vaccination in an animal model," Sok told "The findings allow us to focus on a key aspect that allowed the cows to achieve this: the long loops that enable broad neutralization of HIV."

The Nature paper comes months after a team of researchers led by Duke University found that adding more targets to the experimental human RV144 HIV vaccine dramatically increased protection. The upgraded vaccine design, used this time in monkeys, showed a more than 55% protection rate against the simian-human immunodeficiency virus (SHIV), compared with the 31.2% efficacy of the RV144 vaccine.

According to Sok, the Nature research team is interested in conducting a few more HIV immunization experiments to see whether they "can redirect antibody responses to other epitopes."