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rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
1999-8-9
pubmed:abstractText
We have designed liposomal diepitope constructs that allow the physical combination, within the same vesicle, of B and Th epitopes as structurally separate entities. The immune response against such constructs was explored using TPEDPTDPTDPQDPSS (TPE), a B cell epitope originating from a Streptococcus mutans surface adhesin and QYIKANSKFIGITEL (QYI), a "universal" Th epitope from tetanus toxin. The two peptides were linked to the outer surface of small (diameter approximately 100 nm) unilamellar liposomes by covalent conjugation to two different anchors. To that end we have developed a strategy that allows the controlled chemical coupling of TPE and QYI, functionalized at their N terminus with a thiol, to preformed liposomes containing thiol-reactive derivatives of phosphatidylethanolamine and the lipopeptide S-[2,3-bis (palmitoyloxy)-(2-RS)-propyl]-N-palmitoyl-(R)-cysteinyl-alanyl-gly cine (Pam3CAG), respectively. This synthetic construct (administered i.p. to BALB/c mice) induced highly intense (titers > 20,000), anamnestic and long-lasting (over 2 years) immune responses, indicating that this strategy is successful. Two parameters were of prime importance to elicit this response with our liposomal diepitope constructs: (1) the simultaneous expression of B and Th epitopes on the same vesicle, and (2) the lipopeptide Pam3CAG anchor of the Th epitope QYI could not be replaced by a phosphatidylethanolamine anchor (a lesser immune response was observed). Analysis of the antibody response revealed a complex pattern; thus, besides the humoral response (production of IgG1, IgG2a, IgG2b) a superposition of a T-independent (TI-2 type) response was also found (IgM and IgG3). These results indicate that liposomal diepitope constructs could be attractive in the development of synthetic peptide-based vaccines.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0014-2980
pubmed:author
pubmed:issnType
Print
pubmed:volume
29
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2297-308
pubmed:dateRevised
2003-11-14
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Design of highly immunogenic liposomal constructs combining structurally independent B cell and T helper cell peptide epitopes.
pubmed:affiliation
Laboratoire de Chimie Bioorganique, Université Louis Pasteur, Faculté de Pharmacie, Strasbourg-Illkirch, France.
pubmed:publicationType
Journal Article