The disruption of LPS in Salmonella Typhimurium provides partial protection against Salmonella Choleraesuis as a live attenuated vaccine

Vaccine. 2023 Sep 22;41(41):5951-5956. doi: 10.1016/j.vaccine.2023.08.078. Epub 2023 Sep 4.

Abstract

Interference with the normal synthesis of LPS was shown to enhance immune responses to conserved outer membrane proteins. In the present study, we have constructed three vaccine candidates by deleting four genes (rfaL, rfbB, rffG and wzy) associated with LPS synthesis in the wild-type strain UK-1. Virulence assessment showed that after oral immunization of BALB/c mice, all mutant strains were attenuated and had significantly reduced ability to colonize host tissues compared to the wild-type strain. In addition, all three vaccine candidates induced elevated humoral, mucosal and cellular immune responses against S. Typhimurium and S. Choleraesuis OMPs compared to the PBS-treated group. Finally, immunization of mice with the rSC0136 vaccine candidate strain provided 100 % and 40 % protection against S. Typhimurium and S. Choleraesuis challenge, respectively. These results suggest that the deletion of LPS synthesis-related genes may be an effective strategy against homologous serotypes, but provides only partial protection against heterologous serotypes.

Keywords: Cross-protection; Lipopolysaccharides (LPS); Salmonella Choleraesuis; Salmonella Typhimurium; Vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Lipopolysaccharides
  • Mice
  • Mice, Inbred BALB C
  • Salmonella enterica*
  • Salmonella typhimurium* / genetics
  • Vaccines, Attenuated

Substances

  • Vaccines, Attenuated
  • Lipopolysaccharides

Supplementary concepts

  • Salmonella enterica subsp. enterica