title: Prime-boost vaccine regimen confers protective immunity to human-derived enterotoxigenic Escherichia coli.
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.
authors.affiliation: Microbiology Department, Biomedical Science Institute, University of São Paulo, Av Prof. Lineu Prestes 1374, São Paulo 05508-000, Brazil.
authors.forename: M O
authors.initials: MO
authors.lastname: Lasaro
authors.forename: W B
authors.initials: WB
authors.lastname: Luiz
authors.forename: M E
authors.initials: ME
authors.lastname: Sbrogio-Almeida
authors.forename: L C S
authors.initials: LC
authors.lastname: Ferreira
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology; D004195:Disease Models, Animal; D004403:Dysentery / Q000276:immunology / Q000517:prevention & control*; D004926:Escherichia coli / Q000276:immunology; D004927:Escherichia coli Infections / Q000276:immunology / Q000517:prevention & control*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000276:immunology; D022361:Escherichia coli Vaccines / Q000008:administration & dosage / Q000276:immunology*; D005243:Feces; D005260:Female; D036781:Fimbriae Proteins / Q000235:genetics / Q000276:immunology; D006801:Humans; D007117:Immunization, Secondary; D007070:Immunoglobulin A / Q000032:analysis; D007074:Immunoglobulin G / Q000097:blood; D051379:Mice; D008892:Milk / Q000276:immunology; D012486:Salmonella typhimurium / Q000235:genetics / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology
chemical_list: D000942:Antigens, Bacterial; D001428:Bacterial Vaccines; D029968:Escherichia coli Proteins; D022361:Escherichia coli Vaccines; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic; C022924:colonization factor antigens; D036781:Fimbriae Proteins