EVALUATION OF LIPID-BASED DELIVERY SYSTEMS FOR INDUCTION OF MUCOSAL AND SYSTEMIC IMMUNE RESPONSES: EFFECT OF CpG MOTIFS
Date
2004-12
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
ORCID
Type
Degree Level
Doctoral
Abstract
CpG oligodeoxynucleotides (ODNs) are potent adjuvants that significantly enhance cellular and humoral responses to coadministered antigens when given parenterally or by mucosal routes. However, in vivo degradation of ODNs limits their uptake and their effectiveness as adjuvants.
The purpose of these studies was to investigate the ability of biphasic lipid vesicles (VTA) to enhance the adjuvant activity of CpG ODNs following systemic administration and to evaluate the feasibility of non-invasive methods for vaccine delivery such as mucosal and transcutaneous immunization.
Results showed that formulation of CpG ODN in VTA significantly enhanced its adjuvanticity and protected pigs against infection with Actinobacillus pleuropneumoniae without induction of the severe tissue damage seen with the commercial adjuvant VSA. The dose of CpG ODN required to induce protective immune responses in pigs when formulated in VTA was also established.
The present studies also showed that administration of antigen and CpG ODN in biphasic lipid vesicles resulted in induction of systemic and local antibody responses after immunization with a combined mucosal/systemic approach, while the protein either alone or with CpG ODN did not induce mucosal immune responses.
The mechanism by which these biphasic lipid vesicles may enhance the adjuvant effect of CpG ODN include: 1) increasing its availability by preventing dilution and degradation in vivo, 2) improving its uptake by antigen presenting cells (APCs) due to the particulate nature of lipid-based formulations. The least effective combinations induced mild or no inflammation, while formulations--- containing both the antigen and CpG ODN induced cell infiltration 24 and 48 h after administration, suggesting that cellular infiltration may be essential for the induction of immune responses.
The ability of microneedles to facilitate the delivery of antigens after topical administration was also evaluated in these studies and the data presented clearly showed that only with previous application of microneedles, topical administration of CT induces systemic and mucosal immunity in pigs.
Description
Keywords
LIPID-BASED DELIVERY SYSTEMS, MUCOSAL AND SYSTEMIC IMMUNE RESPONSES, EFFECT OF CpG MOTIFS
Citation
Degree
Doctor of Philosophy (Ph.D.)
Department
Pharmacy and Nutrition