A novel adjuvanted capsule based strategy for oral vaccination against infectious diarrhoeal pathogens

Christopher J.H. Davitt, Edel A. McNeela, Stephanie Longet, Joshua Tobias, Vincenzo Aversa, Craig P. McEntee, Monica Rosa, Ivan S. Coulter, Jan Holmgren, Ed C. Lavelle

Research output: Contribution to journalArticlepeer-review

27 Citations (Scopus)

Abstract

Diarrhoeal infections are a major cause of morbidity and mortality with enterotoxigenic Escherichia coli (ETEC) and cholera imposing a significant global burden. There is currently no licensed vaccine for ETEC. Development of new nonliving oral vaccines has proven difficult due to the physicochemical and immunological challenges associated with the oral route. This demands innovative delivery solutions to protect antigens, control their release and build in immune-stimulatory activity. We describe the Single Multiple Pill® (SmPill®) vaccine formulation which combines the benefits of enteric polymer coating to protect against low gastric pH, a dispersed phase to control release and aid the solubility of non-polar components and an optimized combination of adjuvant and antigen to promote mucosal immunity. We demonstrate the effectiveness of this system with whole cell killed E. coli overexpressing colonization factor antigen I (CFA/I), JT-49. Alpha-galactosylceramide was identified as a potent adjuvant within SmPill® that enhanced the immunogenicity of JT-49. The bacteria associated with the dispersed phase were retained within the capsules at gastric pH but released at intestinal pH. Vaccination with an optimized SmPill® formulation promoted CFA/I-specific immunoglobulin A (IgA) responses in the intestinal mucosa in addition to serum IgG and a solubilized adjuvant was indispensable for efficacy.

Original languageEnglish
Pages (from-to)162-173
Number of pages12
JournalJournal of Controlled Release
Volume233
DOIs
Publication statusPublished - 10 Jul 2016

Keywords

  • Adjuvant
  • Capsule
  • Enteric
  • Oral delivery
  • Traveller's diarrhoea
  • Vaccine

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