title: Oral immunization of mice with gamma-irradiated Brucella neotomae induces protection against intraperitoneal and intranasal challenge with virulent B. abortus 2308.
abstract: Brucella spp. are Gram-negative, facultative intracellular coccobacilli that cause one of the most frequently encountered zoonosis worldwide. Humans naturally acquire infection through consumption of contaminated dairy and meat products and through direct exposure to aborted animal tissues and fluids. No vaccine against brucellosis is available for use in humans. In this study, we tested the ability of orally inoculated gamma-irradiated B. neotomae and B. abortus RB51 in a prime-boost immunization approach to induce antigen-specific humoral and cell mediated immunity and protection against challenge with virulent B. abortus 2308. Heterologous prime-boost vaccination with B. abortus RB51 and B. neotomae and homologous prime-boost vaccination of mice with B. neotomae led to the production of serum and mucosal antibodies specific to the smooth LPS. The elicited serum antibodies included the isotypes of IgM, IgG1, IgG2a, IgG2b and IgG3. All oral vaccination regimens induced antigen-specific CD4(+) and CD8(+) T cells capable of secreting IFN-γ and TNF-α. Upon intra-peritoneal challenge, mice vaccinated with B. neotomae showed the highest level of resistance against virulent B. abortus 2308 colonization in spleen and liver. Experiments with different doses of B. neotomae showed that all tested doses of 10(9), 10(10) and 10(11) CFU-equivalent conferred significant protection against the intra-peritoneal challenge. However, a dose of 10(11) CFU-equivalent of B. neotomae was required for affording protection against intranasal challenge as shown by the reduced bacterial colonization in spleens and lungs. Taken together, these results demonstrate the feasibility of using gamma-irradiated B. neotomae as an effective and safe oral vaccine to induce protection against respiratory and systemic infections with virulent Brucella.
authors.affiliation: Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, Indiana, United States of America.
authors.forename: Neha
authors.initials: N
authors.lastname: Dabral
authors.affiliation: Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, Indiana, United States of America; Departamento de Inmunología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Mexico City, Mexico.
authors.lastname: Martha-Moreno-Lafont
authors.affiliation: Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Tech, Virginia, United States of America.
authors.forename: Nammalwar
authors.initials: N
authors.lastname: Sriranganathan
authors.affiliation: Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, Indiana, United States of America.
authors.forename: Ramesh
authors.initials: R
authors.lastname: Vemulapalli
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology; D002002:Brucella / Q000276:immunology* / Q000528:radiation effects*; D002004:Brucella Vaccine / Q000008:administration & dosage / Q000276:immunology*; D002003:Brucella abortus / Q000276:immunology*; D002006:Brucellosis / Q000517:prevention & control*; D003429:Cross Reactions / Q000276:immunology; D004195:Disease Models, Animal; D018985:Epitopes, B-Lymphocyte / Q000276:immunology; D005260:Female; D005720:Gamma Rays; D007114:Immunization; D007132:Immunoglobulin Isotypes / Q000097:blood / Q000276:immunology; D007274:Injections, Intraperitoneal; D051379:Mice
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D002004:Brucella Vaccine; D018985:Epitopes, B-Lymphocyte; D007132:Immunoglobulin Isotypes