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pubmed-article:12023344pubmed:abstractTextFour HLA-DR-restricted HIV-derived Th lymphocyte (HTL) epitopes cross-reactive with the murine I-A(b) class II molecule were used to evaluate different vaccine design strategies to simultaneously induce multiple HTL responses. All four epitopes were immunogenic in H-2(b) mice, demonstrating the feasibility of murine models to evaluate epitope-based vaccines destined for human use. Immunization with a pool of peptides induced responses against all four epitopes; illustrating immunodominance does not prevent the induction of balanced multispecific responses. When different delivery systems were evaluated, a multiple Ag peptide construct was found to be less efficient than a linear polypeptide encompassing all four epitopes. Further characterization of linear polypeptide revealed that the sequential arrangement of the epitopes created a junctional epitope with high affinity class II binding. Disruption of this junctional epitope through the introduction of a GPGPG spacer restored the immunogenicity against all four epitopes. Finally, we demonstrate that a GPGPG spacer construct can be used to induce HTL responses by either polypeptide or DNA immunization, highlighting the flexibility of the approach.lld:pubmed
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pubmed-article:12023344pubmed:articleTitleA rational strategy to design multiepitope immunogens based on multiple Th lymphocyte epitopes.lld:pubmed
pubmed-article:12023344pubmed:affiliationEpimmune, San Diego, CA 92121, USA. blivingston@epimmune.comlld:pubmed
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pubmed-article:12023344pubmed:publicationTypeResearch Support, U.S. Gov't, P.H.S.lld:pubmed
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