What if preventing millions of deaths in children every year were as simple as a little transgenic technology and a favorite food that's a dime a dozen, proverbially speaking? To Peter Lachmann, at the University of Cambridge in England, it might be just that straightforward.
Lachmann is convinced that antibody-enriched egg whites may be the key to wide-scale protection against diarrheal disease. The transgenic technology could be poised to deliver, thanks to the work of avian geneticists such as Helen Sang at the Roslin Institute in Scotland. But this clever recipe for passive immunity might take decades of prep time.
Each year, diarrheal diseases kill two million children under the age of five in the developing world. (Click here for related story.) Lachmann hopes that antibodies present in transgenic eggs would linger in the intestines of such children and coat the toxins produced by gut-living pathogens such as enterotoxic Escherichia coli and Shigella, two major causes of diarrheal illness. "What stimulated me to think about this [was] the work of Helen Sang, who had the ingenious method of putting (antibodies) into egg whites," he says.
In her lab outside Edinburgh, Sang has spent more than a decade trying to turn hens into therapeutic protein factories. "It's always been difficult because manipulating the egg is hard," she says. Her team had moderate success when they injected DNA directly into the zygote, but she and her colleagues have since found lentiviruses to be capable and useful vehicles. They now use these self-inactivating vectors, derived from equine infectious anemia virus, to enter the chicken embryo and deliver a transgene encoding a therapeutic protein - say, an antibody - linked to an albumin regulatory sequence. When this embryo grows up to be a rooster, Sang's team can mate him with a wild-type female to produce hens that will lay antibody-fortified eggs. The gene stays put across generations of breeding, and gene silencing is minimal, Sang says. Last year, her team successfully produced egg whites containing humanized single-chain antibodies with the potential to treat malignant melanoma (PNAS, 104:1771-6, 2007).
Fortified foods are nothing new, as any cereal lover can attest. Neither is sharing antibodies - whether they are passed from mother to child, or taken from pooled blood donations, or from convalescent or recently immunized patients. For the past few decades, scientists have been trying to immunize or breed animals to secrete certain antibodies into their milk. Though there have been successes (Adv Exp Med Biol, 606:321-43, 2008), the costs of the operation, and paltry concentrations of antibody in the milk, have been formidable stumbling blocks, Lachmann says.
What antibody would be up for Lachmann's particular challenge? He points to camel antibodies, which carry their specificity entirely on their heavy chain, rendering the light chain unnecessary (it's easier to produce one protein than two). According to Sang and Lachmann, camel antibodies should be able to withstand the harsh acidic environment of the stomach and resist the proteases they'd encounter on their perilous journey down the human digestive tract.
The idea is still a bit undercooked, in part because it's unclear how preparing the egg white for human consumption would leave the antibody intact. Swallowed antibodies have a limited life span of three weeks at most, since egg-eaters lack cells to produce more antibody, so kids would have to eat the eggs fairly often to get continuous protection, says Lachmann, who studies microbial immunity.
Clifford Lo, a nutrition researcher at Harvard Medical School (where this author is based) and Children's Hospital in Boston, notes that he is "interested in the concepts involved" in this project, but doubts "the protection would last" from a weekly transgenic egg. Plus, there's the cost associated with a regular supply of transgenic animals and eggs, and many cases of childhood diarrhea stem from viral sources, not bacterial. "Probably the most important factor is ensuring a safe, clean water supply," he notes in an e-mail.