Defective vaccine-induced immunity to Schistosoma mansoni in P strain mice. I. Analysis of antibody responses.

Abstract

Inbred P4 strain mice have previously been shown to be uniquely defective in their resistance to challenge infection induced by irradiated cercariae of Schistosoma mansoni. To assess whether the low levels of resistance developed by vaccinated P mice could be due to a defective antibody response, we compared the anti-schistosomulum antibody responses in vaccinated P animals with those occurring in vaccinated C57BL/6J (B6) mice, a strain that consistently develops high levels of resistance to challenge infection. Our results indicate that vaccinated P mice develop levels of total anti-schistosomulum antibodies that are significantly lower than those occurring in B6 mice for at least 15 wk after immunization, with the exception of the fifth week, at which time the responses are indistinguishable. Further analysis revealed that the defect in P strain antibody response occurs specifically in the IgM isotype and that specific IgM levels in P mice are less than one-half the levels in B6 mice at every time point examined. In contrast, no differences in total IgM immunoglobulins were evident when sera from normal (nonvaccinated) P and B6 mice were compared. P mouse anti-schistosomulum IgG antibody responses reached the same levels as those observed in B6 mice by 5 wk after vaccination. However, a much faster decay in IgG antibody levels occurred after this time point in P animals. No differences were observed when the levels of anti-schistosomulum antibodies occurring in each of the major IgG isotypes (IgG1, IgG2a, IgG2b, IgG3) were compared in sera from P and B6 mice vaccinated 4 wk previously. Similarly, vaccinated P and B6 mice were found to mount indistinguishable IgG anamnestic responses after challenge infection. Finally, no differences between vaccinated P and B6 mice were observed when immediate (30 min) skin test and mast cell degranulation responses to a soluble schistosome antigenic preparation were compared. The above findings suggest that P strain mice have a specific defect in their ability to mount IgM antibody responses after immunization with irradiated cercariae. The possible contribution of this defect in IgM response to the decreased resistance of vaccinated P mice to challenge infection is discussed.