title: Cross-priming of T cell responses by synthetic microspheres carrying a CD8+ T cell epitope requires an adjuvant signal.
abstract: Controlling the cross-presentation of exogenous Ags to CD8+ T cells represents a major step for designing new vaccination strategies. Whereas several recombinant pseudo-viral particles have been used as delivery systems for triggering potent CTL responses to heterologous exogenous Ags, the adjuvant properties of virus-like particles (VLPs) themselves were little questioned. Here, we analyzed the contribution of the porcine parvovirus (PPV)-VLPs to the induction of protective cellular responses to exogenous Ags carried by an independent delivery system. Microspheres, which are known to transfer exogenous Ags into the MHC class I pathway, were chosen for delivering the immunodominant OVA(257-264) CD8+ T cell epitope (B-OVAp). This delivery system fulfills the requirements in terms of cross-presentation, but fails to induce cross-priming of specific CD8+ T cells. Coinjection of PPV-VLPs with B-OVAp results in the priming of potent CTL responses and type 1-biased immunity in a CD4- and CD40-independent manner, as efficiently as the recombinant PPV-VLPs carrying the same epitope (PPV-OVAp). Furthermore, vaccination with PPV-VLPs and B-OVAp was fully efficient to protect mice against the development of OVA-bearing melanoma. These findings indicate that PPV-VLPs act not only as a delivery system but also as a strong adjuvant when independently provided with exogenous Ag. Thus, dissociation between delivery system and adjuvant would provide a more flexible and reliable system to induce potent and protective CTL.
authors.affiliation: Unité de Biologie des Régulations Immunitaires, Institut Pasteur, Institut National de la Santé et de la Recherche Médicale E352, Paris, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Boisgérault
authors.forename: Paloma
authors.initials: P
authors.lastname: Rueda
authors.forename: Cheng Ming
authors.initials: CM
authors.lastname: Sun
authors.forename: Sandra
authors.initials: S
authors.lastname: Hervas-Stubbs
authors.forename: Marie
authors.initials: M
authors.lastname: Rojas
authors.forename: Claude
authors.initials: C
authors.lastname: Leclerc
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D019013:CD40 Antigens / Q000235:genetics / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology; D004527:Egg Proteins / Q000008:administration & dosage / Q000276:immunology; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000378:metabolism; D016056:Immunodominant Epitopes / Q000008:administration & dosage*; D007155:Immunologic Factors / Q000008:administration & dosage; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008863:Microspheres; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D028323:Parvovirus, Porcine / Q000276:immunology; D010446:Peptide Fragments; D015398:Signal Transduction; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D019013:CD40 Antigens; D004527:Egg Proteins; D000949:Histocompatibility Antigens Class II; D016056:Immunodominant Epitopes; D007155:Immunologic Factors; C110366:OVA-8; D010446:Peptide Fragments; D010047:Ovalbumin