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Cross-Priming of T Cell Responses by Synthetic Microspheres Carrying a CD8⁺ T Cell Epitope Requires an Adjuvant Signal¹

Florence Boisgérault^*, Paloma Rueda, Cheng Ming Sun^*, Sandra Hervas-Stubbs^*, Marie Rojas^* and Claude Leclerc^2,*

^* Unité de Biologie des Régulations Immunitaires, Institut Pasteur, and Institut National de la Santé et de la Recherche Médicale E352, Paris, France; and Immunología y Génetica Aplicada, Madrid, Spain

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.

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