Famously, the word vaccine comes from the Latin word for cow — a namesake that traces back to the late 1700s.
Now cows are once again at the cutting edge of vaccine science. Thanks to a quirk of how cows make antibodies, they are helping researchers understand human immunity. Someday, cows could serve as testing grounds for whether vaccines are well-designed. And it’s possible that cow antibodies could treat everything from autoimmunity to infectious disease.
A new study on HIV by scientists at Scripps Research Institute explores these possibilities. Cows don’t get HIV, but, when injected with viral proteins, produce antibodies that block HIV infection. The results, which were reported Thursday in Nature, are part of a larger effort to make the first HIV vaccine.
HIV mutates constantly, creating many strains. Broadly neutralizing antibodies are key to an HIV vaccine because they could protect against these various strains. But they’ve proven hard to make in people.
“The body in HIV infection — either from natural infection or in response to a vaccine — does not like to make broadly neutralizing antibodies,” said Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases. “It just doesn’t do it readily, and it doesn’t do it very well.”
So scientists are keenly interested in other animals that might do it well. Enter cows: Two separate teams of scientists at Scripps made two parallel discoveries in recent years — that broadly neutralizing antibodies for HIV are especially long and gangly, and that cows’ normal antibodies are also long and gangly.
That was the inspiration for this study. “It was an alignment of the stars, where we had veterinarians, cow antibody scientists, and HIV scientists all talking and came up with this … relatively simple question to test,” said Devin Sok, the study’s first author and director for antibody discovery and development at the International AIDS Vaccine Initiative.
The scientists injected four cows with a protein that mimics HIV’s surface, known as the envelope. They then drew blood samples over the course of a year and isolated antibodies. The antibodies were tested in a dish for their ability to block HIV from infecting cells.
What they found surprised them. Within two months, all the cows made antibodies that blocked a variety of viral strains — much faster than in people. And low doses of antibody were enough to block the virus.
“We definitely didn’t expect to get the [antibody] response that we did. We didn’t expect the extent of the response or how quick the response developed,” said Sok. “That was kind of mind-blowing.”
As to why cows are such good antibody factories, it may have to do with their unique stomachs. Dr. Vaughn Smider, professor of molecular medicine at Scripps, points out that cows’ four-chambered stomachs hold a whopping 20 gallons of digestive microbes. “The cow immune system has to deal with keeping in check all these microorganisms,” said Smider. Cows’ extra-long antibodies “can potentially bind into grooves, crevices, or areas where a typical antibody from humans or mice may not be able to bind.”
The study is the first to reliably elicit broadly neutralizing antibodies. But Dr. John Mascola, director of vaccine research at NIAID, cautions that there are still obstacles to an effective vaccine in humans.
“The study … doesn’t tell us how to make a vaccine for HIV in people, but it does tell us how the virus evades the human immune response,” said Mascola.
Mascola believes that HIV vaccine research is at “the end of the beginning.” To complete the journey, scientists will need to make a vaccine that accurately mimics HIV’s envelope and coaxes the immune system to make the right antibodies. Barton Haynes, director of the Duke Human Vaccine Institute, believes cows could help with the first of those two challenges.
“There is a debate going on about whether this envelope or that envelope … is good,” said Haynes. “Cows may be a really good model to test that.”
Cow HIV antibodies could also be directly given to people. This is not a substitute for a vaccine, which creates long-term immunity to prevent disease. But the antibodies could provide short-term protection or reduce virus levels in those already infected.
To do this, scientists would take antibody-producing cells from cows, isolate their antibody genes, and transfer them into cell lines that grow easily in a lab, such as E. coli or yeast. They would then tinker with the antibodies to make them more “human-like.” This has already been done with mouse antibodies to create drugs such as alemtuzumab, used to treat leukemia.
Smider hopes that, within five to 10 years, cow antibodies will be used for a variety of diseases. He says that their unusual structures could help treat certain cancers, autoimmune disorders, and infectious diseases — such as malaria. Smider is currently working with three different drug companies on this goal.
Another possibility is to milk cows for their antibodies — literally. Cow’s milk is rich in antibodies, and there is evidence that drinking milk from cows immunized against various germs can protect against illness. Immuron, an Australian biotech company, makes a pill prepared with powdered milk from immunized cows to protect against traveler’s diarrhea. The product is available over-the-counter in multiple countries, including the U.S., Canada, Australia, and China.