Murine immunization with CS21 pili or LngA major subunit of enterotoxigenic Escherichia coli (ETEC) elicits systemic and mucosal immune responses and inhibits ETEC gut colonization

Abstract

CS21 pili of enterotoxigenic Escherichia coli (ETEC) is one of the most prevalent ETEC colonization factors. CS21 major subunit, LngA, mediates ETEC adherence to intestinal cells, and contributes to ETEC pathogenesis in a neonatal mouse infection model. The objectives of this work were to evaluate LngA major subunit purified protein and CS21 purified pili on immunogenicity and protection against ETEC colonization of mice intestine. Recombinant LngA purified protein or purified CS21 pili from E9034A ETEC strain were evaluated for immunogenicity after immunization of C57BL/6 mice. Specific anti-LngA antibodies were detected from mice serum, feces, and intestine fluid samples by ELISA assays. Protection against gut colonization was evaluated on immunized mice orally challenged with wild type E9034A ETEC strain and by subsequent quantification of bacterial colony forming units (CFU) recovered from feces. Recombinant LngA protein and CS21 pili induced specific humoral and mucosal anti-LngA antibodies in the mouse model. CS21 combined with CT delivered intranasally as well as LngA combined with incomplete Freund adjuvant delivered intraperitoneally inhibited ETEC gut colonization in a mouse model. In conclusion, both LngA purified protein and CS21 pili from ETEC are highly immunogenic and may inhibit ETEC intestinal shedding. Our data on immunogenicity and immunoprotection indicates that CS21 is a suitable vaccine candidate for a future multivalent vaccine against ETEC diarrhea.

Intestinal Pathogenic Escherichia coli: Insights for Vaccine Development

“…By contrast, CS21 plus CT as adjuvant was more effective when administered intranasally. This study supports the idea of using CF as a promising antigen and shows that administration routes play an important role in eliciting an effective immune response and protection (Zhang et al, 2016 ).…”

Characterization of enterotoxigenic Escherichia coli strains isolated from the massive multi-pathogen gastroenteritis outbreak in the Antofagasta region following the Chilean earthquake, 2010

“…A C C E P T E D M A N U S C R I P T 8 most commonly detected virulence genes representing antigens that protect against ETEC colonization in murine models (Roy et al, 2009;Zhang et al, 2015). Given their broad distribution and immunogenicity, these protective antigens could complement existing canonical approaches to vaccine development centered on other colonization factors (Vidal et al, 2009).…”

In silico Designing of an Epitope-Based Vaccine Against Common E. coli Pathotypes

“…Many trials have been performed to generate an effective vaccine for various E. coli pathotypes. Regarding intestinal E. coli, Shiga toxin-based vaccine (10), attenuated bacteria-based vaccine (11), and polysaccharide-based vaccine (12) have been proposed for EHEC while autotransporter-based vaccine (13) and adhesion based vaccine (14) were proposed for ETEC. Moving to extraintestinal E. coli, capsular-based vaccine (15) and iron scavenger receptors-based vaccine (16) were designed.…”