Development of a novel S. Typhi and Paratyphi A outer membrane vesicles based bivalent vaccine against enteric fever

Abstract

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.

Establishment of an intragastric surgical model using C57BL/6 mice to study the vaccine efficacy of OMV-based immunogens againstHelicobacter pylori

“…OMV immunization ultimately leads to a reduction in bacterial colonization in immunized animals but not in nonimmunized animals. The serum bactericidal assay results showed that our immunized animal sera killed H. pylori in the presence of complement compared to the nonimmunized animal sera (31,64,65).…”

Paratyphoid Fever A: Infection and Prevention

“…The OMVs have received increasing attention as a vaccine delivery platform in recent years. Howlader et al (2018) developed an oral bivalent typhoid vaccine by mixing the OMVs from S. Typhi and S. Paratyphi A in a 1:1 formulation. Oral immunization of BALB/c mice with the bivalent OMVs at a 2-week interval elicited strong responses of mucosal immunity, humoral immunity and cell-mediated immunity.…”

“…Oral immunization of BALB/c mice with the bivalent OMVs at a 2-week interval elicited strong responses of mucosal immunity, humoral immunity and cell-mediated immunity. The vaccination protected the immunized mice from the lethal challenges of S. Typhi as well as S. Paratyphi A (Howlader et al, 2018).…”

Mucosal vaccines and technology

“…Formulations of Neisseria meningitidis OMVs (VA-MENGOC-BC, MenBvac, MeNZB and Bexero) have been successfully used to vaccinate both adults and children and to control outbreaks of meningococcal B infection in several countries [100,101]. OMVs from other Gram-negative pathogens are also promising vaccine candidates, including those from Salmonella [102], Shigella flexneri [103] and V. cholerae [104]. However, their potential for unintended toxicity due to associated toxins is a safety concern and limits their widespread use, although chemical detoxification can overcome this, but at the loss of immunogenicity and adjuvanticity [105].…”