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

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• 作者：Christopher J.H. Davitt^a ; ¹ ; Edel A. McNeela^a ; ¹ ; Stephanie Longet^a ; ¹ ; Joshua Tobias^b ; Vincenzo Aversa^c ; Craig P. McEntee^a ; Monica Rosa^c ; Ivan S. Coulter^c ; Jan Holmgren^b ; Ed C. Lavelle^a ; ^d ; ^{lavellee@tcd.ie" class="auth_mail" title="E-mail the corresponding author}
• 关键词：AUC ; area under the curve ; BSA ; bovine serum albumin ; CF ; colonization factor ; CFA ; colonization factor antigen ; CT ; cholera toxin ; EDTA ; ethylenediaminetetraacetic acid ; ETEC ; enterotoxigenic Escherichia coli ; FITC ; fluorescein isothiocyanate ; GEMS ; Global Enterics Multicenter Study ; GFP ; green fluorescent protein ; GIT ; gastrointestinal tract ; IEC ; intestinal epithelial cell ; iNKT ; invariant natural killer T cell ; JT-227 ; CFA/I-positive ETEC strain expressing GFP ; JT-49 ; E.coli K12 strain overe
• 刊名：Journal of Controlled Release
• 出版年：2016
• 出版时间：10 July 2016
• 年：2016
• 卷：233
• 期：Complete
• 页码：162-173
• 全文大小：2442 K

文摘

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.