Recent progress toward an enterotoxigenic Escherichia coli vaccine

Abstract

Enterotoxigenic Escherichia coli(ETEC) is the most common cause of bacterial diarrhea in children in Africa, Asia and Latin America and in travelers to these regions. Despite this, no effective vaccine for ETEC is available. ETEC causes disease by colonizing the small intestine with colonization factors, most of which are fimbriae, and production of heat-labile and/or heat-stable enterotoxins. Antibodies against heat-labile enterotoxin and the colonization factors have been shown to be protective, and local immunity in the gut seems to be of prime importance for protection. Hence, several inactivated and live candidate ETEC vaccines consisting of toxin antigens, alone or together with colonization factors, have been evaluated in clinical trials. In this review, the authors describe ETEC vaccine development in progress and the rationale for constructing different types of vaccines. They also discuss possibilities of enhancing immune responses to candidate ETEC vaccines, particularly in children.

Keywords::

• adjuvants
• colonization factors
• enterotoxins
• enterotoxigenic Escherichia coli
• heat-labile enterotoxin
• heat-stable enterotoxin
• mucosal immunity
• oral vaccines

Acknowledgements

The authors thank all colleagues, staff and volunteers at Gothenburg, Sweden, for participating in the studies of the oral inactivated Enterotoxigenic Escherichia coli vaccines, and colleagues J Holmgren at the University of Gothenburg, N Carlin and B Gustafsson at ETVAX, and AL Bourgeois et al. at the PATH Enteric Vaccine Initiative program for valuable advice. They also thank their colleagues at icddr,b in Dhaka, F Qadri et al. for excellent collaboration in many of the studies described in this review.

Financial & competing interests disclosure

The studies of the prototype and tetravalent inactivated whole cell Enterotoxigenic Escherichia coli vaccines were supported by PATH’s Enteric Vaccine Initiative program, a grant from the Sahlgrenska Academy, University of Gothenburg and the Swedish for Research Council. A-M Svennerholm is a shareholder of Gotovax AB, Gothenburg, Sweden, which collaborates with ETVAX AB, Stockholm, Sweden, and PATH, Seattle, USA, on the development of the tetravalent LCTBA-colonization factor Enterotoxigenic Escherichia coli vaccine. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Notes

^†Two oral doses given in bicarbonate buffer 2 weeks apart.

CF: Colonization factor; CTB: Cholera toxin B subunit; dmLT: Double-mutated heat-labile enterotoxin; ETEC: Enterotoxigenic Escherichia coli; LT: Heat-labile enterotoxin; LTB: Heat-labile enterotoxin B subunit.