A February edition of the journal Science reports on the slow, disappointing progress in creating a vaccine to control the human disease schistosomiasis, which the World Health Organization considers the second most devastating parasitic disease in the underdeveloped world, second only to malaria. If such a critical worm vaccine for humans is coming “only at a snail’s pace,” as the author complains, then what progress can we expect on the perennial question for cattle producers: Are we ever going to see a vaccine that will work against the common cattle worms?
A pair of Belgian parasitologists, Manuela Rinaldi and Peter Geldhof, take up that question in an issue last year of the journal Parasite Immunology. The duo reviews the studies that have been going on for more than a quarter century now yet yielded no commercial application. Why the delay?
- Every cow/calf producer knows cattle grow resistant to worms with age. But decades of scientific studies attempting to understand why that immunity occurs still haven’t bought us a clear picture of why and how the bovine’s immune mechanisms function against worms. Scientists do know that exposure to the brown stomach worm increases levels of immune-system components that signal a humoral response is occuring, much like exposure to a virus. However, the way in which those antibodies actually contribute to the protection against Ostertagia still isn’t clear. Plus, worm infection also causes cellular changes that signal the parasite may actually be able to suppress the cellular immune response of the animal. Some studies suggest Ostertagia may be able to fool the animal’s regulatory T cell system—the immune bodies that keep the immune response in check and prevent the system from attacking the body itself—and thus remain invisible to the immune system. Finally, the immune response is variable in animals of different genetics, Rinaldi and Geldhof point out. They cite one recent study that quantified two chromosomal segments contributing to resistance against worms, raising the possibility that genetic markers may one day be available to improve seedstock selection for worm immunity.
- Because it’s a relatively complex organism compared to a virus or bacteria, understanding how a stomach worm interacts with the host animal at the molecular level demands a good knowledge of the genetic make-up of not just the calf, but of the parasite, as well. At the time they were writing their review, the authors note, about 7,000 genetic tags clustered in 2,300 genes had been identified for Ostertagia—but that’s less than 20 percent of the entire expected genome of the species. Right now, geneticists lack functional genetic tools to type the organism, the parasite can’t be bred in the laboratory, and it can’t even be cultured for long periods of time.
- One of the main reasons for the the slow progress toward a vaccine characterized by the limited number of research studies is the obvious high cost of performing infection trials in cattle. The more than 50 studies published on immune responses against intestinal nematode infections in mice in just the last year double the number of studies done in cattle over the past two decades. Researchers have made great strides in understanding effective anthelmintic responses in rodent models, but for now there are no good infection models that help them translate that knowledge into natural hosts, human or bovine.
- Where to from here? DNA sequencing on a large enough scale to genetically engineer worm vaccines is no longer insurmountable, they believe. Advances in the study of proteins, sugars and fats at the molecular level have made it easier to study parasite and host immune interactions at a level of detail never before dreamed of. In addition, the ability of today’s computers to build mathematical models that can predict “short cuts” to identify potential new antiparasitics or vaccine candidates has brought them closer. However, although the technology is promising, Rinaldi and Geldhof take note that none of the studies using recombinant antigens they reviewed have successfully reduced worm or egg count burdens when used in infected cattle.