A -Based Vaccine Formulation Reduces Vertical Transmission and Leads to Enhanced Pup Survival in a Pregnant Neosporosis Mouse Model.

The apicomplexan parasite is the worldwide leading cause of abortion and stillbirth in cattle. An attenuated mutant strain (Lm3Dx) was engineered by deleting the virulence genes , , and in order to avoid systemic infection and to target the vector to antigen-presenting cells (APCs). Insertion of , coding for the major surface protein NcSAG1 of , yielded the vaccine strain Lm3Dx_NcSAG1. The efficacy of Lm3Dx_NcSAG1 was assessed by inoculating 1 × 10, 1 × 10, or 1 × 10 CFU of Lm3Dx_NcSAG1 into female BALB/c mice by intramuscular injection three times at two-week intervals, and subsequent challenge with 1 × 10 tachyzoites of the highly virulent NcSpain-7 strain on day 7 of pregnancy. Dose-dependent protective effects were seen, with a postnatal offspring survival rate of 67% in the group treated with 1 × 10 CFU of Lm3Dx_NcSAG1 compared to 5% survival in the non-vaccinated control group. At euthanasia (25 days post-partum), IgG antibody titers were significantly decreased in the groups receiving the two higher doses and cytokines recall responses in splenocyte culture supernatants (IFN-γ, IL-4, and IL-10) were increased in the vaccinated groups. Thus, Lm3Dx_NcSAG1 induces immune-protective effects associated with a balanced Th1/Th2 response in a pregnant neosporosis mouse model and should be further assessed in ruminant models.