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Abstract: Strategies using epitope-based vaccination are being considered for melanoma immunotherapy, in an attempt to overcome failure of other modalities. In the present study, we designed and produced a multiepitope polypeptide for melanoma (MEP-mel), which contains three repeats of four antigenic epitopes (gp100: 209–217 (210M); gp100: 280–288 (288V); Mart1: 26–35 (27L); tyrosinase: 368–376 (370D). The peptides were attached to each other by linkers containing sequences recognized by the proteasome, to improve protein cleavage and antigen presentation. The results show that peptide-specific T cells produced IFN-γ when stimulated with MEP-mel-transfected dendritic cells. The presentation of peptides by MEP-mel-transfected dendritic cells was proteasome-dependent and was more long-lasting than the presentation of exogenously delivered native peptides. When dendritic cells were loaded with MEP-mel protein, weak cross presentation was induced. The production of multiepitope molecules based on several peptides linked by sequences sensitive to proteasomal cleavage represents a promising new tool for the improvement of cancer immunotherapy. [Copyright &y& Elsevier]

Systemically administered DNA encoding a recombinant human immunodeficiency virus (HIV) derived immunogen effectively primes a cytotoxic T lymphocyte (CTL) response in macaques. In this further pilot study we have evaluated mucosal delivery of DNA as an alternative priming strategy. Plasmid DNA, pTH.HW, encoding a multi-CTL epitope gene, was incorporated into poly(d,l-lactic-co-glycolic acid) microparticles of less than 10 μm in diameter. Five intrarectal immunizations failed to stimulate a circulating vaccine-specific CTL response in 2 Mamu-A*01+ rhesus macaques. However, 1 week after intradermal immunization with a cognate modified vaccinia virus Ankara vaccine MVA.HW, CTL responses were detected in both animals that persisted until analysis postmortem, 12 weeks after the final boost. In contrast, a weaker and less durable response was seen in an animal vaccinated with the MVA construct alone. Analysis of lymphoid tissues revealed a disseminated CTL response in peripheral and regional lymph nodes but not the spleen of both mucosally primed animals. [Copyright &y& Elsevier]

Chlamydia psittaci is the pathogen of psittacosis, and it has emerged as a significant public health threat. Because most infections are easily overlooked, a vaccine is recognized as the best solution to control the spread of C. psittaci. Our previous study showed that Pgp3 protein is efficacious as a subunit vaccine while not the best candidate due to the negative effects. Thus, in this study, we tested the ability of a tandem epitope vaccine candidate designated SP based on Pgp3-dominant epitopes to induce protective immunity against pulmonary chlamydial infection. BALB/c mice were intraperitoneally inoculated with multiepitope peptide antigens followed by intranasal infection with C. psittaci. We found that the multiepitope peptide antigens induced strong humoral and cellular immune responses with high Th1-related (IFN-γ and IL-2) and proinflammatory (IL-6) cytokine levels. Meanwhile, the pathogen burden and inflammatory infiltration were significantly reduced in lungs of SP-immunized mice after chlamydial challenge. In addition, the IFN-γ and IL-6 secretion levels in the infected lungs were substantially reduced. Overall, our findings demonstrate that the peptide vaccine SP plays a significant role with good immunogenicity and protective efficacy against C. psittaci lung infection in BALB/c mice, providing important insights towards understanding the potential of peptide vaccines as new vaccine antigens for inducing protective immunity against chlamydial infection. • Construct a Pgp3 mutiepitope vaccine SP based on bioinformatics analysis. • The peptide vaccine induced strong humoral and cellular immune responses. • The peptide vaccine shows good protective efficacy against C. psittaci lung infection. • Provides important insights towards understanding the potential of peptide vaccines. [ABSTRACT FROM AUTHOR]