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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2001-2-22
pubmed:abstractText
The highly purified saponin derivative, QS-21, from the Quillaja saponaria Molina tree has been proved to be safe for parenteral administration and represents a potential alternative to bacterial enterotoxin derivatives as a mucosal adjuvant. Here we report that p.o. administration of QS-21 with the vaccine protein tetanus toxoid elicited strong serum IgM and IgG Ab responses, which were only slightly enhanced by further oral immunization. The IgG Ab subclass responses were predominantly IgG1 followed by IgG2b for the 50-microg p.o. dose of QS-21, whereas the 250-microg p.o. dose also induced IgG2a and IgG3 Abs. Low oral QS-21 doses induced transient IgE Ab responses 7 days after the primary immunization, whereas no IgE Ab responses were seen in mice given the higher QS-21 dose. Further, low but not high p.o. QS-21 doses triggered Ag-specific secretory IgA (S-IgA) Ab responses. Th cell responses showed higher IFN-gamma (Th1-type) and lower IL-5, IL-6, and IL-10 (Th2-type) secretion after the high QS-21 p.o. dose than after low doses. Interestingly, the mucosal adjuvant activity of low oral QS-21 doses was diminished in IL-4(-/-) mice, suggesting a role for this cytokine in the initiation of mucosal immunity by oral QS-21. In summary, our results show that oral QS-21 enhances immunity to coadministered Ag and that different doses of QS-21 lead to distinct patterns of cytokine and serum Ab responses. We also show that an early IL-4 response is required for the induction of mucosal immunity by oral QS-21 as adjuvant.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
166
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2283-90
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:11160283-Adjuvants, Immunologic, pubmed-meshheading:11160283-Administration, Oral, pubmed-meshheading:11160283-Animals, pubmed-meshheading:11160283-Antibodies, Bacterial, pubmed-meshheading:11160283-Dose-Response Relationship, Immunologic, pubmed-meshheading:11160283-Drug Administration Schedule, pubmed-meshheading:11160283-Immunity, Active, pubmed-meshheading:11160283-Immunity, Mucosal, pubmed-meshheading:11160283-Immunoglobulin A, Secretory, pubmed-meshheading:11160283-Immunoglobulin G, pubmed-meshheading:11160283-Immunoglobulin M, pubmed-meshheading:11160283-Injections, Subcutaneous, pubmed-meshheading:11160283-Interleukin-4, pubmed-meshheading:11160283-Intestinal Mucosa, pubmed-meshheading:11160283-Mice, pubmed-meshheading:11160283-Mice, Inbred C57BL, pubmed-meshheading:11160283-Mice, Knockout, pubmed-meshheading:11160283-Saponins, pubmed-meshheading:11160283-T-Lymphocytes, Helper-Inducer, pubmed-meshheading:11160283-Tetanus Toxoid
pubmed:year
2001
pubmed:articleTitle
Oral QS-21 requires early IL-4 help for induction of mucosal and systemic immunity.
pubmed:affiliation
Department of Microbiology, University of Alabama, Medical Center, Birmingham, AL 35294, USA. prosper@uab.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't