How Cow Antibodies Are Helping Scientists Develop an HIV Vaccine

HIV is a tenacious virus, but cows are able to quickly produce antibodies that fight infection, giving researchers insights on how to develop an effective human vaccine.

Researchers have long sought to develop an effective HIV vaccine. Several treatments have undergone clinical trials, but the only one that’s been even slightly successful, a 2009 study in Thailand, lowered HIV infection rates by only 30 percent.

But scientists haven’t given up hope.

An effective HIV vaccine could be “transformative,” Anthony Fauci, the director of the National Institute of Allergy and Infectious Disease, said in May. Fauci said modeling from the National Institutes of Health showed that even if a vaccine was only 50 percent effective, it could reduce the number of people living with HIV by 36 percent around the world in 15 years.

Last week, researchers released a study showing progress toward developing an effective vaccine. In their paper, which was published in the journal Nature, they describe their success in prompting a quick immune response to HIV — at least in four cows.

While it may seem a big leap from cows to humans, scientists are encouraged by the results.

Vaccines are made from the same germs that cause a disease. A vaccine is potent enough to prompt an immune response, but not so strong that it causes a recipient to become sick. When exposed to small amounts of a virus, a person’s immune system produces antibodies, which are proteins designed to kill the virus. Even after the virus goes away, the immune cells “remember” it and are able to produce antibodies quickly if a person is exposed to the virus again.

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This tried-and-true method, which has helped to combat polio, measles, and the flu, hasn’t worked with HIV because the virus replicates very quickly, leading to dozens of different strains and substrains, and can remain latent in the body for long periods of time.

Antibodies that successfully combat HIV do exist, but only in about 10-20 percent of people infected with HIV. And they often take a long time to develop. When exposed to most viruses, people produce antibodies within a few days. But with HIV, it often takes more than two years.

“One of, if not the major challenge in development of a safe and effective HIV vaccine, is the inability to elicit broadly neutralizing antibodies in humans,” Wayne Koff, president and CEO of the Human Vaccines Project, said in an email. Koff was not affiliated with the new study.

The goal of developing an effective vaccine hinges on prompting a person’s immune system to begin quickly producing what are called broadly neutralizing antibodies (bNAbs) in order to fight off infection.

And that’s where the cows come in.

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The researchers, supported by NIH, thought cows might yield insights on fighting HIV when they looked at the structure of human bNAbs that were produced by people with long-term HIV infections. Specifically, they looked at a looped area on the antibodies called HCDR3.

One of the distinct features of the HIV virus is that it is surrounded by a thick envelope of sugars, called the glycan shield, that is hard for normal-sized antibodies to penetrate. The scientists realized that in the small percent of humans that do produce HIV bNAbs those antibodies have extra-long HCDR3 loops that can pierce through the glycan shield.

Antibodies in cows also have naturally long HCDR3 loops, though no one is quite sure why. One theory is, because cows have multiple stomachs with lots of bacteria, they need extra-powerful antibodies to protect them from infection.

The researchers injected the four cows with an HIV immunogen, a molecule that can prompt the HIV immune response. To their surprise, not only did the cows produce HIV bNAbs, but they produced them quickly — within 35 to 50 days. At just over a year, one cow produced bNAbs against 117 strains of HIV.

“These new data are very interesting and encouraging,” said Dan Barouch, director of the Center for Virology and Vaccine Research at Harvard Medical School. “Although cows are not humans, these data provide important insights on how the immune system responds to HIV [immunogens],” Barouchs did not take part in the research.

The scientists who undertook the study say they hope that their findings will pave the way for greater understanding of how the human immune system responds to HIV.

"HIV is a human virus," Devin Sok of the Department of Immunology and Microbiology at The Scripps Research Institute said in a press release, "but researchers can certainly learn from immune responses across the animal kingdom."

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