1. Field of the Invention
The present invention relates to a vaccine for protection of mammals from disease caused by Neospora caninum. More specifically, the invention relates to safe and immunogenically effective vaccines for protection of bovines and canines from abortion caused by Neospora caninum. 
2. Brief Description of the Prior Art
Neospora caninum was first reported by Dubey et al (JAVMA, Vol. 192, No. 9, May 1, 1988) as a Toxoplasmosis-like illness affecting dogs. Neospora caninum was found to be structurally distinct from Toxoplasma gondii and did not react with anti-T. gondii antiserum in an immunoperoxidase test. Dubey et al described the major lesions associated with the organism as meningoencephalomyelitis and myositis. Within the past few years, neosporosis has become recognized as a major reproductive disease in cattle (Anderson et al., 1994, Food Animal Practice, 10: 439-461) with cases reported in North and South America, Europe, Africa, the Pacific-rim countries as well as in the United States. The major clinical manifestation of bovine neosporosis is fetal abortion, with focal nonsuppurative necrotizing encephalitis, nonsuppurative myocarditis, and myositis in the fetus (Anderson et al., 1991, Journal of the American Veterinary Medical Association, 198: 241-244). According to Anderson et al., 1997 (Journal of the Veterinary Medical Association, 210: 1169-1172), retrospective studies of cattle in California indicate that neosporosis has been endemic since at least 1985. These authors state that 18 to 19% of all aborted bovine fetuses submitted to the California Veterinary Diagnostic Laboratory System have Neospora sp infection. In a prospective survey of selected dairies in California, the number of abortions attributed to Neospora sp infections was even greater (42.5%).
Ho et al (J. Parasitol., 1997, 83(3)) have recently reported the successful reproduction of bovine abortion and fetal infection by infecting pregnant cows with tachyzoites of Neospora caninum. This publication suggests that there may be a correlation between serological titer as measured by indirect fluorescent antibody (IFA) testing and protection from abortion caused by Neospora caninum in cows. Cows with IFA titers of 320 and 640 did not abort after infection with tachyzoites of this organism.
As mentioned previously, neosporosis has also been reported in puppies and in dogs as old as 15 years of age. The percentage of infected dogs that show clinical signs is unknown. In dogs, Neospora caninum can infect any tissue, although it is most commonly found in the central nervous system and spinal nerve roots. The most severe infections are seen in puppies that were infected in utero. These puppies exhibit ascending paralysis. Abortion can be reproduced in experimental infection of pregnant bitches during the early stage of gestation. Sulfonamides, pyrimethamine and clindamycin have been used to treat neosporosis in dogs.
Neospora caninum can also produce a fatal infection in experimentally inoculated cats. However, the disease has not yet been reported to occur naturally in cats.
Neosporosis has been observed to cause abortion in sheep and goats but to a lesser extent than is found in cattle. Experimental infection is readily induced in sheep and goats by subcutaneous injection of tachyzoites.
Although neosporosis, especially in cattle, appears to pose an increasingly serious problem and there is certainly a long felt need to solve this problem by protecting mammals using a vaccine, there are no descriptions of vaccines, vaccine development nor suggestions of methods of preparing vaccines to protect cattle and other animals from disease caused by Neospora caninum.