Portal de Periódicos da CAPES

A Rational Strategy to Design Multiepitope Immunogens Based on Multiple Th Lymphocyte Epitopes

2002; American Association of Immunologists; Volume: 168; Issue: 11 Linguagem: Inglês

10.4049/jimmunol.168.11.5499

1550-6606

Brian Livingston, Claire Crimi, Mark J. Newman, Yuichiro Higashimoto, Ettore Appella, John Sidney, Alessandro Sette,

Monoclonal and Polyclonal Antibodies Research

Abstract Four HLA-DR-restricted HIV-derived Th lymphocyte (HTL) epitopes cross-reactive with the murine I-Ab class II molecule were used to evaluate different vaccine design strategies to simultaneously induce multiple HTL responses. All four epitopes were immunogenic in H-2b 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.