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Journal of Virology, January 2008, p. 785-794, Vol. 82, No. 2
0022-538X/08/$08.00+0     doi:10.1128/JVI.01811-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Novel Plant Virus-Based Vaccine Induces Protective Cytotoxic T-Lymphocyte-Mediated Antiviral Immunity through Dendritic Cell Maturation{triangledown}

Patrick Lacasse,1 Jérôme Denis,2,{dagger} Réjean Lapointe,3 Denis Leclerc,2 and Alain Lamarre1*

Immunovirology Laboratory, Institut National de la Recherche Scientifique, INRS-Institut Armand-Frappier, 531 Boulevard des Prairies, Laval, Québec, Canada H7V 1B7,1 Centre de Recherche en Infectiologie, Pavillon CHUL, Université Laval, 2705 Boulevard Laurier, Québec, Québec, Canada G1V 4G2,2 Centre de Recherche, CHUM, Hôpital Notre-Dame, Université de Montréal and Institut du Cancer de Montréal, 2099 Rue Alexandre-de-Sève, Montréal, Québec, Canada H2L 4M13

Received 17 August 2007/ Accepted 27 September 2007

Currently used vaccines protect mainly through the production of neutralizing antibodies. However, antibodies confer little or no protection for a majority of chronic viral infections that require active involvement of cytotoxic T lymphocytes (CTLs). Virus-like particles (VLPs) have been shown to be efficient inducers of cell-mediated immune responses, but administration of an adjuvant is generally required. We recently reported the generation of a novel VLP system exploiting the self-assembly property of the papaya mosaic virus (PapMV) coat protein. We show here that uptake of PapMV-like particles by murine splenic dendritic cells (DCs) in vivo leads to their maturation, suggesting that they possess intrinsic adjuvant-like properties. DCs pulsed with PapMV-like particles displaying the lymphocytic choriomeningitis virus (LCMV) p33 immunodominant CTL epitope (PapMV-p33) efficiently process and cross-present the viral epitope to p33-specific transgenic T cells. Importantly, the CTL epitope is also properly processed and presented in vivo, since immunization of p33-specific T-cell receptor transgenic mice with PapMV-p33 induces the activation of large numbers of specific CTLs. C57BL/6 mice immunized with PapMV-p33 VLPs in the absence of adjuvant develop p33-specific effector CTLs that rapidly expand following LCMV challenge and protect vaccinated mice against LCMV infection in a dose-dependent manner. These results demonstrate the efficiency of this novel plant virus-based vaccination platform in inducing DC maturation leading to protective CTL responses.

* Corresponding author. Mailing address: INRS-Institut Armand-Frappier, 531 Boul. des Prairies, Laval, Québec, Canada H7V 1B7. Phone: (450) 687-5010, ext. 4262. Fax: (450) 686-5308. E-mail: alain.lamarre{at}iaf.inrs.ca

{triangledown} Published ahead of print on 7 November 2007.

{dagger} Present address: Pegase Medical Inc., 2954 Boul. Laurier, Suite 310, Québec, Québec, Canada G1V 4T2.

Journal of Virology, January 2008, p. 785-794, Vol. 82, No. 2
0022-538X/08/$08.00+0     doi:10.1128/JVI.01811-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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