A novel fusion protein domain III-capsid from dengue-2, in a highly aggregated form, induces a functional immune response and protection in mice

Journal Article · Wed Nov 25 00:00:00 EST 2009 · Virology

DOI:https://doi.org/10.1016/j.virol.2009.08.029· OSTI ID:21357565

Valdes, Iris ^[1]; Bernardo, Lidice ^[2]; Gil, Lazaro ^[1]; Pavon, Alekis ^[2]; Lazo, Laura; Lopez, Carlos; Romero, Yaremis; Menendez, Ivon; Falcon, Viviana; Betancourt, Lazaro; Martin, Jorge; Chinea, Glay; Silva, Ricardo ^[1]; Guzman, Maria G ^[2]; Guillen, Gerardo; Hermida, Lisset ^[1]

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1. Vaccine Division, Center for Genetic Engineering and Biotechnology (CIGB), Ave 31, P.O. Box 6162, Havana 6, 10 600 (Cuba)
2. PAHO/WHO Collaborating Center for the study of Dengue and its vector, Department of Virology, 'Pedro Kouri' Tropical Medicine Institute (IPK), P.O. Box. 601, Havana (Cuba)

Based on the immunogenicity of domain III from the Envelope protein of dengue virus as well as the proven protective capacity of the capsid antigen, we have designed a novel domain III-capsid chimeric protein with the goal of obtaining a molecule potentially able to induce both humoral and cell-mediated immunity (CMI). After expression of the recombinant gene in Escherichia coli, the domain III moiety retained its antigenicity as evaluated with anti-dengue sera. In order to explore alternatives for modulating the immunogenicity of the protein, it was mixed with oligodeoxynucleotides in order to obtain particulated aggregates and then immunologically evaluated in mice in comparison with non-aggregated controls. Although the humoral immune response induced by both forms of the protein was equivalent, the aggregated variant resulted in a much stronger CMI as measured by in vitro IFN-gamma secretion and protection experiments, mediated by CD4{sup +} and CD8{sup +} cells. The present work provides additional evidence in support for a crucial role of CMI in protection against dengue virus and describes a novel vaccine candidate against the disease based on a recombinant protein that can stimulate both arms of the acquired immune system.

• OSTI ID: 21357565
• Journal Information: Virology, Vol. 394, Issue 2; Other Information: DOI: 10.1016/j.virol.2009.08.029; PII: S0042-6822(09)00517-0; Copyright (c) 2009 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; ISSN 0042-6822
• Country of Publication: United States
• Language: English

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