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

Artikel i vetenskaplig tidskrift
Författare C. J. H. Davitt
E. A. McNeela
S. Longet
Joshua Tobias
V. Aversa
C. P. McEntee
M. Rosa
I. S. Coulter
Jan Holmgren
E. C. Lavelle
Publicerad i Journal of Controlled Release
Volym 233
Sidor 162-173
ISSN 0168-3659
Publiceringsår 2016
Publicerad vid Institutionen för biomedicin, avdelningen för mikrobiologi och immunologi
Sidor 162-173
Språk en
Länkar dx.doi.org/10.1016/j.jconrel.2016.0...
Ämnesord Vaccine, Oral delivery, Adjuvant, Traveller's diarrhoea, Enteric, Capsule, enterotoxigenic escherichia-coli, vibrio-cholerae, etec vaccine, b-subunit, developing-countries, colonization factors, antibody-responses, enteric infections, immune-responses, mucosal, vaccines, Chemistry, Pharmacology & Pharmacy
Ämneskategorier Mikrobiologi

Sammanfattning

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 (R) (SmPill (R)) 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 (R) 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 (R) 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.

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