A multi-epitope fusion antigen candidate vaccine for Enterotoxigenic Escherichia coli is protective against strain B7A colonization in a rabbit model

• Published in: PLoS neglected tropical diseases 2022-02, Vol.16 (2), p.e0010177-e0010177
• Main Authors: Jones, Jr, Richard M, Seo, Hyesuk, Zhang, Weiping, Sack, David A
• Format: Article
• Language: English
• Subjects: Adhesins; Animals; Antibodies; Antibodies, Bacterial - blood; Antigens; Antigens, Bacterial - administration & dosage; Antigens, Bacterial - genetics; Antigens, Bacterial - immunology; Bacteria; Biology and Life Sciences; Cholera; Colonization; Control; Developing countries; Diarrhea; Diarrhea - blood; Diarrhea - microbiology; Diarrhea - prevention & control; Disease control; Disease Models, Animal; E coli; Enterotoxigenic Escherichia coli - genetics; Enterotoxigenic Escherichia coli - growth & development; Enterotoxigenic Escherichia coli - immunology; Epitopes; Epitopes - genetics; Epitopes - immunology; Escherichia coli; Escherichia coli infections; Escherichia coli Infections - blood; Escherichia coli Infections - microbiology; Escherichia coli Infections - prevention & control; Escherichia coli Vaccines - administration & dosage; Escherichia coli Vaccines - genetics; Escherichia coli Vaccines - immunology; Humans; Immune response; Immunization; Infections; Intestine; Intestine, Small - immunology; Intestine, Small - microbiology; Intestines; LDCs; Medical research; Medicine and Health Sciences; Pathology; Prevention; Protection; Proteins; Rabbits; Research and Analysis Methods; Small intestine; Strains; Testing; Toxins; Tropical diseases; Vaccines; Varieties; Viral vaccines
• ISSN: 1935-2735; 1935-2727; 1935-2735
• DOI: 10.1371/journal.pntd.0010177

Enterotoxigenic Escherichia coli (ETEC) strains are a leading cause of children's and travelers' diarrhea. Developing effective vaccines against this heterologous group has proven difficult due to the varied nature of toxins and adhesins that determine their pathology. A multivalent candidate vaccine was developed using a multi-epitope fusion antigen (MEFA) vaccinology platform and shown to effectively elicit broad protective antibody responses in mice and pigs. However, direct protection against ETEC colonization of the small intestine was not measured in these systems. Colonization of ETEC strains is known to be a determining factor in disease outcomes and is adhesin-dependent. In this study, we developed a non-surgical rabbit colonization model to study immune protection against ETEC colonization in rabbits. We tested the ability for the MEFA-based vaccine adhesin antigen, in combination with dmLT adjuvant, to induce broad immune responses and to protect from ETEC colonization of the rabbit small intestine. Our results indicate that the candidate vaccine MEFA antigen elicits antibodies in rabbits that react to seven adhesins included in its construction and protects against colonization of a challenge strain that consistently colonized naïve rabbits.