ILRI's Animal Health Improvement Program in Nairobi is working to develop a novel vaccination strategy that will not only offer better protection against East Coast fever but will do so cheaply and without polluting the environment. Scientists in this program are developing the vaccine potential of a protein found on the surface of the Theileria parva sporozoite-the form of the parasite that ticks pass to cattle.
The scientists have inserted the gene for this parasite protein, named p67 because it has a molecular mass of 67 kilodaltons, into Salmonella bacteria and vaccinia viruses, which produce the foreign protein. Inoculating these harmless recombinant organisms into laboratory animals and cattle has been shown to protect most animals from disease when they are subsequently infected with lethal doses of live parasites.
The success of the p67-based immunisation strategy will depend on how effectively it prevents sporozoite invasion of lymphocytes. Within minutes of entering an animal host, the parasite sporozoites invade lymphocyte cells, where-no longer vulnerable to attack by antibodies-they differentiate into schizont forms. By causing the lymphocytes they invade to multiply uncontrollably, these schizonts quickly kill the animal. Thus, sporozoites that manage to evade initial antibody attack and to enter lymphocytes, can still give rise to fatal disease. To circumvent this parasite survival stratagem, ILRI scientists began looking for a schizont parasite antigen that would augment their sporozoite-antigen vaccine by arming a second branch of the bovine immune system.
Previous ILRI research had shown that animals that recover from East Coast fever possess specialised cells that kill lymphocytes infected with Theileria parva schizonts. These cytotoxic T cells have evolved to recognise and destroy body cells that display 'foreign' proteins, including cancerous cells and cells infected with viruses and parasites.
Employing a series of pioneering molecular and immunological techniques, ILRI scientists have identified two proteins expressed by schizonts that stimulate cytotoxic T-cell responses. The genes encoding these schizont antigens have been cloned, sequenced and inserted into vaccinia viruses, which are now being tested for their vaccine potential. The first experiments have produced exciting results: cattle infected with these recombinant viruses have developed cytotoxic T-cells that kill parasite-infected lymphocytes.
To perfect these live vaccination strategies, ILRI scientists need to enlarge their experimental data. Construction of a new Biologically Secure Animal Disease Research Facility allows them to do this. As the scientific knowledge generated by these more informative experiments grows, so does the prospect of a safe, reliable and cheap vaccine that will keep African cattle-and by extension the farms and households that raise them-healthy and productive.
(ILRI)
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