An enterobacterial common antigen mutant of Salmonella enterica serovar Typhimurium as a vaccine candidate

Int J Med Microbiol. 2015 Sep;305(6):511-22. doi: 10.1016/j.ijmm.2015.05.004. Epub 2015 Jun 1.

Abstract

Due to increasing rates of invasive Salmonella enterica serovar Typhimurium infection, there is a need for an effective vaccine to prevent this disease. Previous studies showed that a mutation in the first gene of the Enterobacterial common antigen biosynthetic pathway, wecA, resulted in attenuation of S. Typhimurium in a murine model of salmonellosis. Furthermore, immunization with a wecA(-) strain protected against lethal challenge with the parental wild type S. Typhimurium strain. Herein, we examined whether the S. Typhimurium wecA(-) strain could also provide cross-protection against non-parental strains of S. Typhimurium and S. Enteritidis. We found that intraperitoneal immunization (IP) with S. Typhimurium SL1344 wecA(-) resulted in a significant increase in survival compared to control mice for all Salmonella challenge strains tested. Oral immunization with SL1344 wecA(-) also resulted in increased survival; however, protection was less significant than with intraperitoneal immunization. The increase in survival of SL1344 wecA(-) immunized mice was associated with a Salmonella-specific IgG antibody response. Furthermore, analysis of sera from IP and orally immunized animals revealed cross-reactive antibodies to numerous Salmonella isolates. Functional analysis of antibodies found within the sera from IP immunized animals revealed agglutination and opsonophagocytic activity against all tested O:4 Salmonella serovars. Together these results indicate that immunization with a S. Typhimurium wecA(-) strain confers protection against lethal challenge with wild type S. Typhimurium and S. Enteritidis and that immunization correlates with functional antibody production.

Keywords: Antibody; Live-attenuated; Salmonella Enteritidis; Salmonella Typhimurium; Vaccine; wecA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Antigens, Bacterial / genetics
  • Antigens, Bacterial / immunology*
  • Bacterial Proteins / genetics*
  • Bacterial Proteins / metabolism
  • Bacterial Vaccines / administration & dosage
  • Bacterial Vaccines / immunology
  • Cross Protection
  • Disease Models, Animal
  • Female
  • Immunoglobulin G / blood
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Salmonella Infections / immunology
  • Salmonella Infections / prevention & control
  • Salmonella typhimurium / genetics
  • Salmonella typhimurium / immunology
  • Serogroup
  • Vaccination
  • Vaccines, Attenuated / immunology

Substances

  • Antigens, Bacterial
  • Bacterial Proteins
  • Bacterial Vaccines
  • Immunoglobulin G
  • Vaccines, Attenuated
  • enterobacterial common antigen