Preclinical optimization of an enterotoxigenic Escherichia coli adjuvanted subunit vaccine using response surface design of experiments

• DOI: 10.1038/s41541-020-00228-w
• Publication Date: 2020-09-11T10:09:21Z
• Authors: David Poncet; Catherine Hessler; Hong Liang; Sylviane Gautheron; Michelle Sergent; Nicholas D. Rintala; Emilie Seydoux; Po-Wei D. Huang; David Argilla; Sophie Ruiz; Jon Heinrichs; Milton Maciel; Mark T. Orr
• Keywords: Enterotoxigenic Escherichia coli; Microfold cell

Enterotoxigenic E. coli (ETEC) is a leading cause of moderate-to-severe diarrhoea. ETEC colonizes the intestine through fimbrial tip adhesin colonization factors and produces heat-stable and/or heat-labile (LT) toxins, stimulating fluid electrolyte release to watery We reported that vaccine containing recombinant factor antigen (CfaEB) targeting I (CFA/I) an attenuated LT toxoid (dmLT) elicited mucosal systemic immune responses against both targets. Additionally, toll-like receptor 4 ligand second-generation lipid adjuvant (TLR4-SLA) induced potent response, dependent on formulation. However, combination components at their respective individual optimal doses may not achieve profile. studied subunit prototype in mice using response surface design experiments (DoE), consisting 64 dose-combinations CfaEB, dmLT SLA four formulations (aqueous, aluminium oxyhydroxide, squalene-in-water stable nanoemulsion [SE] or liposomes saponin Quillaja saponaria-21 [LSQ]). Nine readouts focusing antibody functionality plasma cell were selected profile parenterally administered prototype. The data integrated model identify dosage each component best Compared maximal used mouse models (10 µg 1 5 SLA), reduction up 37%, 60% 88% for SLA, respectively, maintained even maximized responses, with SE LSQ formulations. DoE approach can help determine composition limited number accelerate development multi-antigen/component vaccines.