Flagellin-deficient outer membrane vesicles as adjuvant induce cross-protection of Salmonella Typhimurium outer membrane proteins against infection by heterologous Salmonella serotypes

Int J Med Microbiol. 2018 Oct;308(7):796-802. doi: 10.1016/j.ijmm.2018.06.001. Epub 2018 Jun 8.

Abstract

Salmonella enteric serovar infections result in high morbidity and mortality worldwide. Cross-protective vaccines are an effective strategy in controlling salmonellosis caused by multiple serotypes. In our previous study, outer membrane vesicles (OMVs) derived from flagellin-deficient Salmonella Typhimurium (S. Typhimurium) were proven effective in mediating cross-protection against infection by multiple Salmonella serotypes; OMVs also exhibit potent adjuvant effects. In this study, we further investigated the adjuvant capacities of flagellin-deficient S. Typhimurium OMVs. Our finding showed that outer membrane proteins (OMPs) in combination with flagellin-deficient S. Typhimurium OMVs could function as adjuvants and invoke stronger humoral, cellular, mucosal, and cross-protective immune responses compared to conventional aluminum (alum). Furthermore, as an adjuvant, OMVs could induce significantly higher cellular immune responses and display enhanced cross-protection for OMPs against wild-type virulent Salmonella Choleraesuis and Salmonella Enteritidis challenge. In summary, OMVs function as a potent adjuvant with the capability of conferring greater cross-protection against infection by multiple Salmonella serotypes, and may be of great value as an effective vaccine adjuvant in enteric diseases.

Keywords: Adjuvant; Cross-Protection; Outer membrane vesicle; Salmonella.

MeSH terms

  • Adjuvants, Immunologic*
  • Animals
  • Antibodies, Bacterial / immunology
  • Bacterial Outer Membrane Proteins / immunology*
  • Cell Membrane / genetics
  • Cross Protection / immunology*
  • Female
  • Flagellin / genetics*
  • Gastroenteritis / immunology*
  • Gastroenteritis / microbiology
  • Mice
  • Mice, Inbred BALB C
  • Salmonella Infections, Animal / immunology*
  • Salmonella Infections, Animal / microbiology
  • Salmonella Vaccines / immunology
  • Salmonella typhimurium / immunology*

Substances

  • Adjuvants, Immunologic
  • Antibodies, Bacterial
  • Bacterial Outer Membrane Proteins
  • Salmonella Vaccines
  • Flagellin