Cow antibodies are super infection-fighters

The CDR H3 region is different from any other animal antibody, said Robert Rickert, director of the inflammatory disease program at the Sanford-Burnham Medical Research Institute. While bovine antibodies have been studied before, the difference in this region and its implications hadn't been reported.

"I'm a bit surprised it's been overlooked until now, because people have spent a lot of time comparing how antibodies are made in vertebrates from sharks to humans, Rickert said.

"One of the things that was brought out in the paper is not just the unusual length of the CDRs, but the amino acid sequence," Rickert said. The sequence contains more of the amino acid cysteine, which can form chemical bonds within the CDR between each cysteine's sulfur atoms.

These disulfide bridges give rigidity to the CDRs, "so they're not just flapping around," Rickert said.

Unlike Wilson and colleagues, Fabrus is not seeking to turn these antibodies into vaccines, indeed, the human immune system may not be capable of making them. Instead, they are researching how to make the antibodies as human therapeutics.

Antibody production is one of biotechnology’s oldest feats. An immune cell that makes the desired antibody is fused with an “immortalized” animal cell that grows indefinitely. The fused cells, called hybridomas, are grown in fermentation tanks, and they churn out exact clones of the antibody. Hence the name, monoclonal antibodies. Examples of monoclonal antibody medicines include Rituxan, for non-Hodgkin’s lymphoma and rheumatoid arthritis; and Avastin, for cancer.

However, antibodies made from cows or other animals can’t be just injected into people; the human immune system would recognize them as foreign and reject them. This happened with some of the first antibody drugs, derived from mice. It took years of effort to learn which parts of the antibodies provoked immune reactions. The rejection-causing parts of the antibody were swapped out with human The result was “chimeric” antibodies, named after the mythical chimera, part human and part animal.

Making humanized or chimeric antibodies from mice is now well understood, and cows have been genetically engineered to make human antibodies. However, tailoring cow antibodies to work in humans hasn’t been done before. Smider said his team now has a fairly good idea of how cows make these antibodies, so he's optimistic that their properties can be grafted onto antibodies the human immune system will accept.


Rickert said prospects are good for making a chimeric antibody with the HD3 feature that works in humans. The CDR regions in chimeric antibodies are grafted onto a human base structure, this is done by swapping in human genes that control production of the antibody base.

"The nature of the binding (to antigens) will be very different, it won't be the same as in mouse or human-based antibodies," Rickert said. "I think the opportunity to have antibodies with enhanced diversity may be greater."


