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International Immunology Advance Access originally published online on August 19, 2009
International Immunology 2009 21(10):1175-1183; doi:10.1093/intimm/dxp082
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© The Japanese Society for Immunology. 2009. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Recombinant nucleocapsid-like particles from dengue-2 virus induce protective CD4+ and CD8+ cells against viral encephalitis in mice

Lázaro Gil1,*, Carlos López1,*, Laura Lazo1, Iris Valdés1, Ernesto Marcos1, Ruby Alonso2, Ailyn Gambe1, Jorge Martín1, Yaremis Romero1, María G. Guzmán3, Gerardo Guillén1 and Lisset Hermida1

1 Vaccines Division, Center for Genetic Engineering and Biotechnology, Ave. 31, PO Box 6162, Playa, Havana 10 600, Cuba
2 Experimental Immunotherapy Department, Center of Molecular Immunology, PO Box 16 040, Playa, Havana 11 600, Cuba
3 Virology Department, Tropical Medicine Institute ‘Pedro Kourí’, PAHO/WHO Collaborating Center for the Study of Dengue and its Vector, Autopista Novia del Mediodía, km 6 1/2, PO Box Marianao 13, Havana 11 600, Cuba

Correspondence to: L. Gil González; E-mail: lazaro.gil{at}cigb.edu.cu

Virus-like particles are a highly effective type of subunit vaccine that mimics the overall structure of virus particles without containing infectious genetic material. In this work, a particulate form of the recombinant capsid protein from dengue-2 was evaluated in mice to determine the level of protection against viral challenge and to measure the antigen-induced cell-mediated immunity (CMI). The nucleocapsid-like particles (NLPs) adjuvanted with alum did not induce antiviral antibodies. However, splenocytes from the immunized animals secreted high levels of IFN-{gamma} upon virus stimulation, and a significant protection rate was achieved after challenge with lethal dengue-2 virus. Finally, both IFN-{gamma} secretion and protection against viral encephalitis were demonstrated to be dependent on CD4+ and CD8+ cells. This study provides new evidences regarding the protective role of the CMI in the mouse model without the induction of neutralizing antibodies. Further studies in non-human primates or humanized mice should be carried out to elucidate the usefulness of the NLPs as a potential vaccine candidate against dengue disease.

Keywords: capsid protein, cell-mediated immunity, dengue virus, virus-like particles

* These authors contributed equally to the work.

Transmitting editor: A. Cooke

Received 3 March 2009, accepted 28 July 2009.


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