Towards an oral influenza vaccine: comparison between intragastric and intracolonic delivery of influenza subunit vaccine in a murine model.
In this paper we investigated to which part of the gastro-intestinal (GI) tract, the upper or lower part, an oral influenza vaccine should be targeted to result in an effective immune response in mice. Our study demonstrates that without adjuvant substantial systemic but low respiratory mucosal immune responses were induced in mice after delivery of influenza subunit vaccine to the upper GI-tract (intragastric) as well as the lower GI-tract (intracolonically). When the vaccine was adjuvanted with Escherichia coli heat-labile enterotoxin (LT) these responses were significantly enhanced. Interestingly, intracolonic administration of vaccine with adjuvant also resulted in enhanced cellular immune responses and the desired Th1-skewing of these responses. Intragastric administration of the adjuvanted vaccine also increased T-helper responses. However, Th1-skewing was absent. In conclusion, the right combination of strong mucosal adjuvant (e.g. LT) and antigen delivery site (e.g. the lower part of the gastro-intestinal tract) might result in effective vaccination via the oral route.
Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands. J.Amorij@rug.nl
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Amorij
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Westra
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Hinrichs
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Huckriede
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Frijlink
D000284:Administration, Oral; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D001427:Bacterial Toxins / Q000008:administration & dosage; D003106:Colon / Q000276:immunology; D004768:Enterotoxins / Q000008:administration & dosage; D029968:Escherichia coli Proteins / Q000008:administration & dosage; D005260:Female; D007114:Immunization; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D013270:Stomach / Q000276:immunology; D022223:Vaccines, Subunit / Q000008:administration & dosage
D000914:Antibodies, Viral; D001427:Bacterial Toxins; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007252:Influenza Vaccines; D007376:Interleukin-2; D022223:Vaccines, Subunit; D015847:Interleukin-4; D007371:Interferon-gamma; C027538:heat-labile enterotoxin, E coli