Prime-boost vaccine regimen confers protective immunity to human-derived enterotoxigenic Escherichia coli

Vaccine. 2005 Mar 31;23(19):2430-8. doi: 10.1016/j.vaccine.2004.11.026.

Abstract

Development of effective vaccines against diarrhea caused by enterotoxigenic Escherichia coli (ETEC) strains is still a priority for those living at or traveling to endemic regions. In this work, we evaluated the protective role of an anti-ETEC vaccine regimen based on parenteral priming with a DNA vaccine, pRECFA, followed by oral boosting with a recombinant attenuated Salmonella Typhimurium vaccine strain, HG3, both encoding the same antigen, the structural subunit (CfaB) of the ETEC CFA/I fimbriae. The DNA-priming Salmonella-boosting protocol enhanced both murine anti-CfaB serum IgG and fecal IgA antibody responses and increased the ability of serum antibodies to inhibit the adhesive properties of the CFA/I fimbriae expressed by live bacteria, as compared to mice immunized with only one vaccine type. Addition of a mucosal adjuvant (LTR192G) to the Salmonella vaccine strain further enhanced the synergic effects of the vaccine regimen on the induced CfaB-specific antibody responses. DBA/2 dams submitted to the prime-boost regimen transferred complete passive protection to suckling neonates challenged with a virulent ETEC strain. Detection of milk anti-CfaB IgA antibodies and protection conferred by vaccinated dams to neonates born from non-vaccinated dams indicated that secretion of antigen-specific IgA is the immune response induced by the protective vaccine regimen. These results demonstrate that priming with a DNA vaccine and boosting with a Salmonella strain enhances both quantitatively and qualitatively the antibody responses to the CfaB antigen and represents an alternative for either active or passive immunization approach to ETEC-associated diarrhea.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Bacterial / genetics
  • Antigens, Bacterial / immunology
  • Bacterial Vaccines / administration & dosage
  • Bacterial Vaccines / immunology
  • Disease Models, Animal
  • Dysentery / immunology
  • Dysentery / prevention & control*
  • Escherichia coli / immunology
  • Escherichia coli Infections / immunology
  • Escherichia coli Infections / prevention & control*
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / immunology
  • Escherichia coli Vaccines / administration & dosage
  • Escherichia coli Vaccines / immunology*
  • Feces
  • Female
  • Fimbriae Proteins / genetics
  • Fimbriae Proteins / immunology
  • Humans
  • Immunization, Secondary*
  • Immunoglobulin A / analysis
  • Immunoglobulin G / blood
  • Mice
  • Milk / immunology
  • Salmonella typhimurium / genetics
  • Salmonella typhimurium / immunology
  • Vaccines, DNA / administration & dosage
  • Vaccines, DNA / immunology*
  • Vaccines, Synthetic / immunology

Substances

  • Antigens, Bacterial
  • Bacterial Vaccines
  • Escherichia coli Proteins
  • Escherichia coli Vaccines
  • Immunoglobulin A
  • Immunoglobulin G
  • Vaccines, DNA
  • Vaccines, Synthetic
  • colonization factor antigens
  • Fimbriae Proteins