Maternal Vaccination with a Fimbrial Tip Adhesin and Passive Protection of Neonatal Mice against Lethal Human Enterotoxigenic Escherichia coli Challenge

Author(s)

Luiz, Wilson B. ^{[1, 2]} ; Rodrigues, Juliana F. ^[2] ; Crabb, Joseph H. ^[3] ; Savarino, Stephen J. ^{[4, 5]} ; Ferreira, Luis C. S. ^[2]

Affiliation

^[1] Univ Estadual Santa Cruz, Dept Biol Sci, Ilheus - Brazil

^[2] Univ Sao Paulo, Inst Biomed Sci, Dept Microbiol, Lab Vaccine Dev, Sao Paulo - Brazil

^[3] ImmuCell Corp, Portland, ME - USA

^[4] Naval Med Res Ctr, Enter Dis Dept, Infect Dis Directorate, Silver Spring, MD 20910 - USA

^[5] Uniformed Serv Univ Hlth Sci, Dept Pediat, Bethesda, MD 20814 - USA

• Document type: Journal article
• Source: Infection and Immunity; v. 83, n. 12, p. 4555-4564, DEC 2015.
• Web of Science Citations: 15

Abstract

Globally, enterotoxigenic Escherichia coli (ETEC) is a leading cause of childhood and travelers' diarrhea, for which an effective vaccine is needed. Prevalent intestinal colonization factors (CFs) such as CFA/I fimbriae and heat-labile enterotoxin (LT) are important virulence factors and protective antigens. We tested the hypothesis that donor strand-complemented CfaE (dscCfaE), a stabilized form of the CFA/I fimbrial tip adhesin, is a protective antigen, using a lethal neonatal mouse ETEC challenge model and passive dam vaccination. For CFA/I-ETEC strain H10407, which has been extensively studied in volunteers, an inoculum of 2 x 10(7) bacteria resulted in 50% lethal doses (LD50) in neonatal DBA/2 mice. Vaccination of female DBA/2 mice with CFA/I fimbriae or dscCfaE, each given with a genetically attenuated LT adjuvant (LTK63) by intranasal or orogastric delivery, induced high antigen-specific serum IgG and fecal IgA titers and detectable milk IgA responses. Neonates born to and suckled by dams antenatally vaccinated with each of these four regimens showed 78 to 93% survival after a 20 x LD50 challenge with H10407, compared to 100% mortality in pups from dams vaccinated with sham vaccine or LTK63 only. Crossover experiments showed that high pup survival rates after ETEC challenge were associated with suckling but not birthing from vaccinated dams, suggesting that vaccine-specific milk antibodies are protective. In corroboration, preincubation of the ETEC inoculum with antiadhesin and antifimbrial bovine colostral antibodies conferred a dose-dependent increase in pup survival after challenge. These findings indicate that the dscCfaE fimbrial tip adhesin serves as a protective passive vaccine antigen in this small animal model and merits further evaluation. (AU)

• FAPESP's process: 10/52167-8 - Control of diarrhea induced by enterotoxigenic Escherichia coli (ETEC) strains: vaccine formulations based on the CFA/I fimbriae, CfaE adhesin, heat-labile toxin (LT), and a new vaccine protection experimental model
• Grantee: Luis Carlos de Souza Ferreira
• Support Opportunities: Regular Research Grants