Optimization of the use of C57BL/6 mice as a laboratory animal model for Neospora caninum vaccine studies

The development and testing of vaccines for Neospora caninum in mice require challenge studies to demonstrate a reduction in clinical signs or prevention of vertical transmission of the parasite after vaccination. Genetic susceptibility to N. caninum varies with the strain of mice. In this study, C57BL/6 mice were evaluated as a model for Neospora vaccine studies. A lethal challenge model was developed and the LD(50) was determined to be 1.5 x 10(7)N. caninum tachyzoites/mouse, delivered intraperitoneally. Brain lesions encountered in sections from sub-lethally challenged mice were scored on the basis of severity and total number of lesions to develop a histopathological scoring system for vaccine efficacy. A vertical transmission model for N. caninum vaccine studies was developed by studying mice that were infected either 2 weeks prior to mating or between days 12 and 14 of pregnancy. It was found that infection prior to mating reduced the average number of pups per litter. DNA extracted from fetal tissue was examined by a N. caninum specific polymerase chain reaction (PCR). The rate of vertical transmission was 0, 100 and 90.5% for the uninfected controls, mice infected during pregnancy and mice infected before mating, respectively. This study demonstrates that the C57BL/6 strain of mice is a good model for N. caninum vaccine studies because it is possible to establish a clear-cut lethal challenge model in C57BL/6 mice and they transmit the disease to their offspring efficiently.