Key result
Insertion of short natural flanking sequences into porcine parvovirus-like particles considerably improved the presentation of the OVA epitope by MHC class I molecules.
Insertion of short natural flanking sequences or flexible linkers improves the processing and presentation of epitopes delivered by PPV-VLPs by MHC class I molecules.
May advance VLP-based epitope vaccines in models; leaves open translation to human immunogenicity.
We have previously developed an antigen-delivery system based on hybrid recombinant porcine parvovirus-like particles (PPV-VLPs) formed by the self-assembly of the VP2 protein of PPV carrying a foreign epitope at its N terminus. In this study, different constructs were made containing a CD8(+) T-cell epitope of chicken ovalbumin (OVA) to analyse the influence of the sequence inserted into VP2 on the correct processing of VLPs by antigen-presenting cells. We analysed the presentation of the OVA epitope inserted without flanking sequences or with either different natural flanking sequences or with the natural flanking sequences of a CD8(+) T-cell epitope from the lymphocytic choriomeningitis virus nucleoprotein, and as a dimer with or without linker sequences. All constructs were studied in terms of level of expression, assembly of VLPs and ability to deliver the inserted epitope into the MHC I pathway. The presentation of the OVA epitope was considerably improved by insertion of short natural flanking sequences, which indicated the relevance of the flanking sequences on the processing of PPV-VLPs. Only PPV-VLPs carrying two copies of the OVA epitope linked by two glycines were able to be properly processed, suggesting that the introduction of flexible residues between the two consecutive OVA epitopes may be necessary for the correct presentation of these dimers by PPV-VLPs. These results provide information to improve the insertion of epitopes into PPV-VLPs to facilitate their processing and presentation by MHC class I molecules.
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Rueda et al. (2004) studied Antigen presentation. Porcine parvovirus-like particles (PPV-VLPs) with flanking sequences vs. PPV-VLPs without flanking sequences was evaluated on Level of expression, assembly of VLPs and ability to deliver the inserted epitope into the MHC I pathway. Insertion of short natural flanking sequences into porcine parvovirus-like particles considerably improved the presentation of the OVA epitope by MHC class I molecules.
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