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

Abstract

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.

Authors:
 [1];  [2];  [1];  [2]; ; ; ; ; ; ; ; ;  [1];  [2]; ;  [1]
  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)
Publication Date:
OSTI Identifier:
21357565
Resource Type:
Journal Article
Resource Relation:
Journal Name: Virology; Journal Volume: 394; Journal 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.
Country of Publication:
United States
Language:
English
Subject:
63 RADIATION, THERMAL, AND OTHER ENVIRONMENTAL POLLUTANT EFFECTS ON LIVING ORGANISMS AND BIOLOGICAL MATERIALS; 60 APPLIED LIFE SCIENCES; ANTIGENS; ESCHERICHIA COLI; IMMUNITY; MICE; OLIGONUCLEOTIDES; PROTEINS; SAFETY; VACCINES; VIRUSES; ANIMALS; BACTERIA; DNA; MAMMALS; MICROORGANISMS; NUCLEIC ACIDS; ORGANIC COMPOUNDS; PARASITES; RODENTS; VERTEBRATES

Citation Formats

Valdes, Iris, E-mail: iris.valdes@cigb.edu.c, Bernardo, Lidice, Gil, Lazaro, Pavon, Alekis, Lazo, Laura, Lopez, Carlos, Romero, Yaremis, Menendez, Ivon, Falcon, Viviana, Betancourt, Lazaro, Martin, Jorge, Chinea, Glay, Silva, Ricardo, Guzman, Maria G., Guillen, Gerardo, and Hermida, Lisset. A novel fusion protein domain III-capsid from dengue-2, in a highly aggregated form, induces a functional immune response and protection in mice. United States: N. p., 2009. Web. doi:10.1016/j.virol.2009.08.029.
Valdes, Iris, E-mail: iris.valdes@cigb.edu.c, Bernardo, Lidice, Gil, Lazaro, Pavon, Alekis, Lazo, Laura, Lopez, Carlos, Romero, Yaremis, Menendez, Ivon, Falcon, Viviana, Betancourt, Lazaro, Martin, Jorge, Chinea, Glay, Silva, Ricardo, Guzman, Maria G., Guillen, Gerardo, & Hermida, Lisset. A novel fusion protein domain III-capsid from dengue-2, in a highly aggregated form, induces a functional immune response and protection in mice. United States. doi:10.1016/j.virol.2009.08.029.
Valdes, Iris, E-mail: iris.valdes@cigb.edu.c, Bernardo, Lidice, Gil, Lazaro, Pavon, Alekis, Lazo, Laura, Lopez, Carlos, Romero, Yaremis, Menendez, Ivon, Falcon, Viviana, Betancourt, Lazaro, Martin, Jorge, Chinea, Glay, Silva, Ricardo, Guzman, Maria G., Guillen, Gerardo, and Hermida, Lisset. Wed . "A novel fusion protein domain III-capsid from dengue-2, in a highly aggregated form, induces a functional immune response and protection in mice". United States. doi:10.1016/j.virol.2009.08.029.
@article{osti_21357565,
title = {A novel fusion protein domain III-capsid from dengue-2, in a highly aggregated form, induces a functional immune response and protection in mice},
author = {Valdes, Iris, E-mail: iris.valdes@cigb.edu.c and Bernardo, Lidice and Gil, Lazaro and Pavon, Alekis and Lazo, Laura and Lopez, Carlos and Romero, Yaremis and Menendez, Ivon and Falcon, Viviana and Betancourt, Lazaro and Martin, Jorge and Chinea, Glay and Silva, Ricardo and Guzman, Maria G. and Guillen, Gerardo and Hermida, Lisset},
abstractNote = {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.},
doi = {10.1016/j.virol.2009.08.029},
journal = {Virology},
number = 2,
volume = 394,
place = {United States},
year = {Wed Nov 25 00:00:00 EST 2009},
month = {Wed Nov 25 00:00:00 EST 2009}
}