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* Institut Pasteur, Unité de Régulation Immunitaire et Vaccinologie, Paris, France;
Institut National de la Santé et de la Recherche Médicale, E 352, Paris, France; and
Inmunología y Genética Apl. S.A., Madrid, Spain
Baculoviruses (BVs) are dsDNA viruses that are pathogenic for insects. They have been used worldwide as selective bioinsecticides and for producing recombinant proteins in insect cells. Surprisingly, despite their widespread use in research and industry and their dissemination in the environment, the potential effects of these insect viruses on the immune responses of mammals remain totally unknown. We show in this study that BVs have strong adjuvant properties in mice, promoting potent humoral and CD8+ T cell adaptive responses against coadministered Ag. BVs also induce the in vivo maturation of dendritic cells and the production of inflammatory cytokines. We demonstrate that BVs play a major role in the strong immunogenicity of virus-like particles produced in the BV-insect cell expression system. The presence of even small numbers of BVs among the recombinant proteins produced in the BV expression system may therefore strengthen the immunological properties of these proteins. This adjuvant behavior of BVs is mediated primarily by IFN-
, although mechanisms independent of type I IFN signaling are also involved. This study demonstrates that nonpathogenic insect viruses may have a strong effect on the mammalian immune system.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by grants from Association pour la Recherche sur le Cancer and European Community (CellProm and Theravac Projects; to C.L.). S.H.-S. was supported by Universidad Pública de Navarra (Spain).
2 Address correspondence and reprint requests to Dr. Claude Leclerc, Régulation Immunitaire et Vaccinologie, Institut National de la Santé et de la Recherche Médicale E 352, Institut Pasteur, 25 rue du Docteur Roux, 75724 Paris Cedex 15, France. E-mail address: cleclerc{at}pasteur.fr
3 Abbreviations used in this paper: BV, baculovirus; AcMNPV, Autographa californica multicapsid nucleopolyhedrovirus; BOVAp, bead coated with the OVA257–264 peptide; BEI, binary ethylenimine; cDC, conventional DC; DC, dendritic cell; DOTAP, N-[1-(2,3-dioleoyloxyl)propyl]-N,N,N-trimethylammoniummethyl sulfate; IP-10, IFN-
-inducible protein-10; LCMV, lymphocytic choriomeningitis virus; MHC-I, MHC class I; MIG, monokine induced by IFN-; ODN, oligonucleotide; pDC, plasmacytoid DC; PPV, porcine parvovirus; SEC, size exclusion chromatography; SFC, spot-forming cell; VLP, virus-like particle; WT, wild type; Sf9, Spodoptera frugiperda.
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  K. R. Jordan, R. H. McMahan, J. Z. Oh, M. R. Pipeling, D. M. Pardoll, R. M. Kedl, J. W. Kappler, and J. E. Slansky Baculovirus-Infected Insect Cells Expressing Peptide-MHC Complexes Elicit Protective Antitumor Immunity J. Immunol., January 1, 2008; 180(1): 188 - 197. [Abstract] [Full Text] [PDF]
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