Failure of Intragastrically Administered Yersinia Pestis Capsular Antigen to Protect Mice against Challenge with Virulent Plague: Suppression of Fraction 1-Specific Antibody Response

Rex E. ThomasDepartment of Biological Sciences, University of Notre Dame, Arthropod-Borne Diseases Section, Laboratory of Vectors and Pathogens, and Laboratory of Persistent Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Notre Dame, Indiana

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Warren J. SimpsonDepartment of Biological Sciences, University of Notre Dame, Arthropod-Borne Diseases Section, Laboratory of Vectors and Pathogens, and Laboratory of Persistent Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Notre Dame, Indiana

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Linda L. PerryDepartment of Biological Sciences, University of Notre Dame, Arthropod-Borne Diseases Section, Laboratory of Vectors and Pathogens, and Laboratory of Persistent Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Notre Dame, Indiana

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Tom G. SchwanDepartment of Biological Sciences, University of Notre Dame, Arthropod-Borne Diseases Section, Laboratory of Vectors and Pathogens, and Laboratory of Persistent Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Notre Dame, Indiana

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We evaluated the Yersinia pestis capsular (fraction 1 [F1]) antigen as a potential oral immunogen in mice. We found that single doses of as much as 0.4 mg of F1, administered by intragastric (ig) intubation, were unprotective and did not stimulate production of detectable levels of specific antibody. Three weekly ig doses resulted in low serum antibody levels that also did not provide protection against challenge with virulent Y. pestis. Assays of type-specific antibody following intubation and subsequent challenge with a subcutaneous inoculation of F1 revealed that the quantity of antigen intubated and the secondary IgG2a antibody levels were inversely related, suggesting the induction of tolerance to intragastrically administered F1 antigen. Transfer of spleen cells from intubated mice to F1 immune recipients failed to demonstrate suppression of specific antibody, indicating that the immune tolerance observed in intubated mice was not due to a T suppressor cell-mediated effect. The results of this study indicate that Y. pestis F1 antigen is not likely to be an efficacious immunogen for oral vaccination of mice against plague.

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