A broadly immunogenic polyvalent multiepitope fusion antigen protein protects against and lethal pulmonary challenges in mice.

There are no licensed vaccines for , a leading cause of children's diarrhea and a common etiology of travelers' diarrhea. To develop a cross-protective vaccine, in this study, we constructed a polyvalent protein immunogen to present conserved immunodominant epitopes of invasion plasmid antigens B (IpaB) and D (IpaD), VirG, GuaB, and Shiga toxins on backbone protein IpaD, by applying an epitope- and structure-based multiepitope-fusion-antigen (MEFA) vaccinology platform, examined protein ( MEFA) broad immunogenicity, and evaluated antibody function against invasion and Shiga toxin cytotoxicity but also protection against lethal challenge. Mice intramuscularly immunized with MEFA protein developed IgG responses to IpaB, IpaD, VirG, GuaB, and Shiga toxins 1 and 2; mouse sera significantly reduced invasion of , serotype 2a, 3a, or 6, and type 1 and neutralized cytotoxicity of Shiga toxins of and Shiga toxin-producing .

A polyvalent multiepitope protein cross-protects against infection in rabbit colonization and passive protection models.

Using epitope- and structure-based multiepitope fusion antigen vaccinology platform, we constructed a polyvalent protein immunogen that presents antigenic domains (epitopes) of toxin-coregulated pilus A, cholera toxin (CT), sialidase, hemolysin A, flagellins (B, C, and D), and peptides mimicking lipopolysaccharide O-antigen on a flagellin B backbone. Mice and rabbits immunized intramuscularly with this polyvalent protein immunogen developed antibodies to all of the virulence factors targeted by the immunogen except lipopolysaccharide. Mouse and rabbit antibodies exhibited functional activities against CT enterotoxicity, CT binding to GM ganglioside, bacterial motility, and in vitro adherence of O1, O139, and non-O1/non-O139 serogroup strains.

Intramuscularly Administered Enterotoxigenic (ETEC) Vaccine Candidate MecVax Prevented H10407 Intestinal Colonization in an Adult Rabbit Colonization Model.

Currently, there are no vaccines licensed for enterotoxigenic Escherichia coli (ETEC), a leading cause of children's diarrhea in developing countries and the most common cause of travelers' diarrhea. A vaccine preventing ETEC bacteria from colonization at small intestines and neutralizing enterotoxin toxicity is expected to be effective against ETEC diarrhea. Protein-based multivalent vaccine candidate MecVax was demonstrated recently to induce antibodies neutralizing heat-labile toxin (LT) and heat-stable toxin (STa) enterotoxicity and inhibiting adherence of seven ETEC adhesins (CFA/I, CS1 to CS6) but also to protect against ETEC toxin-mediated clinical diarrhea in a pig challenge model.