Pathogenic characterization in mice of Neospora caninum isolates obtained from asymptomatic calves

SUMMARYIn this study, we characterized 8 new isolates obtained from healthy but congenitally infected calves using a BALB/c mouse model. Neospora caninum-infected mice survived without exhibiting any clinical signs of disease. Nevertheless, differences among isolates in parasite organ distribution, parasite burden and the severity of histopathological lesions were determined. Mice infected with the Nc-Spain 5H, Nc-Spain 7 and Nc-Spain 9 isolates showed higher parasite burdens and more severe brain lesions during the late phase of infection compared to mice infected with the Nc-Spain 2H, Nc-Spain 3H or Nc-Spain 6 isolates. Furthermore, differences in the immunoglobulin IgG1 and IgG2a isotype kinetics induced by these isolates were observed, with a more rapid IgG2a response seen in mice infected with the Nc-Spain 2H and Nc-Spain 3H isolates. These results confirm the intra-species variability of N. caninum pathogenicity.

Canine Distemper Virus DNA Vaccination Induces Humoral and Cellular Immunity and Protects against a Lethal Intracerebral Challenge

ABSTRACT We have studied the immune responses to the two glycoproteins of the Morbillivirus canine distemper virus (CDV) after DNA vaccination of BALB/c mice. The plasmids coding for both CDV hemagglutinin (H) and fusion protein (F) induce high levels of antibodies which persist for more than 6 months. Intramuscular inoculation of the CDV DNA induces a predominantly immunoglobulin G2a (IgG2a) response (Th1 response), whereas gene gun immunization with CDV H evokes exclusively an IgG1 response (Th2 response). In contrast, the CDV F gene elicited a mixed, IgG1 and IgG2a response. Mice vaccinated (by gene gun) with either the CDV H or F DNA showed a class I-restricted cytotoxic lymphocyte response. Immunized mice challenged intracerebrally with a lethal dose of a neurovirulent strain of CDV were protected. However, approximately 30% of the mice vaccinated with the CDV F DNA became obese in the first 2 months following the challenge. This was not correlated with the serum antibody levels.

Immune complexes can trigger specific, T cell-dependent, autoanti-IgG antibody production in mice.

Immunization of mice with a combination of passively administered syngeneic IgG (anti-p-azophenylarsonate [anti-Ars]) antibody and a soluble, multivalent form of the antibody's corresponding antigen (Limulus polyphemus hemocyanin conjugated with Ars [Lph-Ars]) resulted in specific autoanti-IgG Fc (rheumatoid factor) production. The response was rapid and only anti-IgG of the IgM isotype is found. Because immunization with either the IgG antibody or the antigen alone did not result in rheumatoid antibody production, immune complexes appear to be the active form of the immunogens. Antibody/antigen ratios that resulted in maximal anti-IgG antibody responses were the same as those required for peak in vitro immunoprecipitation, i.e., equivalence. Previous exposure of the mice to the exogenously supplied antigen was not required for the response. The response to immune complexes is specific because mice immunized with IgG2a-containing complexes produced autoanti-IgG2a, while mice immunized with IgG1-containing complexes produced anti-IgG1 with little reactivity to other IgG isotypes. IgG2a blocked in its complement-fixing capacity was more effective in eliciting the anti-IgG2a response than native IgG2a, suggesting a possible role for the complement system in modulating the anti-IgG2a response. Induction of rheumatoid factor production by immune complexes could be induced in xid mice but not in nu/nu mice, indicating T lymphocyte dependence of the response. In contrast, the B lymphocyte activator lipopolysaccharide was able to elicit vigorous rheumatoid factor production in both nu/nu and normal mice, demonstrating that nu/nu mice contain B cells capable of making the response. Rheumatoid antibody produced in the immune complex- or LPS-induced responses is Fc specific and has relatively low affinity for IgG that is not bound to antigen.