Open AccessDevelopment of a novel S. Typhi and Paratyphi A outer membrane vesicles based bivalent vaccine against enteric fever
Author(s) -
Debaki Ranjan Howlader,
Hemanta Koley,
Ritam Sinha,
Suhrid Maiti,
Ushasi Bhaumik,
Priyadarshini Mukherjee,
Shanta Dutta
Publication year - 2018
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0203631
Subject(s) - immunogen , salmonella typhi , microbiology and biotechnology , immune system , virology , biology , antigen , salmonella , bivalent (engine) , immunology , antibody , chemistry , bacteria , escherichia coli , biochemistry , monoclonal antibody , gene , genetics , organic chemistry , metal
Salmonella Typhi and Salmonella Paratyphi A are the leading causative agents of enteric fever which cause morbidity and mortality worldwide. Currently, there is no combination vaccine which could protect infection from both the strains. In this paper, we are focusing on the development of a novel bivalent typhoidal Outer Membrane Vesicles (OMVs) based immunogen against enteric fever. We have isolated Salmonella Typhi and Paratyphi A OMVs and also characterized OMVs associated antigens. Then we immunized adult mice with three doses of our newly formulated bivalent immunogen orally (25 μg/200 μl). After three doses of oral immunization, we found our immunogen could significantly induce humoral response. We have also found serum IgG against LPS, Vi-polysaccharide etc. OMV immunization induces CD4, CD8 and CD19 population in immunized mice spleen. It also induces Th1 and Th17-cell mediated immunity. We also found bivalent OMVs immunization can prevent more than lethal dose of heterologous Salmonella strains mediated systemic infection in adult mice model. We determined that, the protective immune responses depend on the humoral and cell-mediated immune response. Furthermore, we have evaluated the mode of protective immune response carried out by anti-OMVs antibody by significantly inhibiting bacterial motility and mucin penetration ability. Taken together, these findings suggest that our bivalent immunogen could be used as a novel candidate vaccine against enteric fever.