A Tetravalent Formulation Based on Recombinant Nucleocapsid-like Particles from Dengue Viruses Induces a Functional Immune Response in Mice and Monkeys.
Despite the considerable effort that has been invested in elucidating the mechanisms of protection and immunopathogenesis associated with dengue virus infections, a reliable correlate of protection against the disease remains to be found. Neutralizing Abs, long considered the prime component of a protective response, can exacerbate disease severity when present at subprotective levels, and a growing body of data is challenging the notion that their titers are positively correlated with disease protection. Consequently, the protective role of cell-mediated immunity in the control of dengue infections has begun to be studied. Although earlier research implicated cellular immunity in dengue immunopathogenesis, a wealth of newer data demonstrated that multifunctional CD8+T cell responses are instrumental for avoiding the more severe manifestations of dengue disease. In this article, we describe a new tetravalent vaccine candidate based on recombinant dengue virus capsid proteins, efficiently produced in Escherichia coli and purified using a single ion-exchange chromatography step. After aggregation to form nucleocapsid-like particles upon incubation with an oligodeoxynucleotide containing immunostimulatory CpG motifs, these Ags induce, in mice and monkeys, an IFN-γ-secreting cell response that significantly reduces viral load after challenge without the contribution of antiviral Abs. Therefore, this new vaccine candidate may not carry the risk for disease enhancement associated with Ab-based formulations.
Center for Genetic Engineering and Biotechnology, Havana 10 600, Cuba; and lazaro.gil@cigb.edu.cu lisset.hermida@cigb.edu.cu.
Lázaro
L
Gil
Center for Genetic Engineering and Biotechnology, Havana 10 600, Cuba; and.
Karem
K
Cobas
Center for Genetic Engineering and Biotechnology, Havana 10 600, Cuba; and.
Laura
L
Lazo
Center for Genetic Engineering and Biotechnology, Havana 10 600, Cuba; and.
Ernesto
E
Marcos
Center for Genetic Engineering and Biotechnology, Havana 10 600, Cuba; and.
Laura
L
Hernández
Center for Genetic Engineering and Biotechnology, Havana 10 600, Cuba; and.
Edith
E
Suzarte
Pan American Health Organization/World Health Organization Collaborating Center for the Study of Dengue and Its Vector, Department of Virology, Pedro Kourí Tropical Medicine Institute, Havana 17 100, Cuba.
Alienys
A
Izquierdo
Center for Genetic Engineering and Biotechnology, Havana 10 600, Cuba; and.
Iris
I
Valdés
Center for Genetic Engineering and Biotechnology, Havana 10 600, Cuba; and.
Aracelys
A
Blanco
Center for Genetic Engineering and Biotechnology, Havana 10 600, Cuba; and.
Pedro
P
Puentes
Center for Genetic Engineering and Biotechnology, Havana 10 600, Cuba; and.
Yaremis
Y
Romero
Center for Genetic Engineering and Biotechnology, Havana 10 600, Cuba; and.
Yusleidi
Y
Pérez
Pan American Health Organization/World Health Organization Collaborating Center for the Study of Dengue and Its Vector, Department of Virology, Pedro Kourí Tropical Medicine Institute, Havana 17 100, Cuba.
María G
MG
Guzmán
Center for Genetic Engineering and Biotechnology, Havana 10 600, Cuba; and.
Gerardo
0000-0003-3098-0970
G
Guillén
Center for Genetic Engineering and Biotechnology, Havana 10 600, Cuba; and lazaro.gil@cigb.edu.cu lisset.hermida@cigb.edu.cu.
Lisset
L
Hermida
D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D003715:Dengue / Q000276:immunology*; D003716:Dengue Virus / Q000502:physiology*; D004195:Disease Models, Animal; D000882:Haplorhini; D006801:Humans; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000378:metabolism*; D051379:Mice; D019590:Nucleocapsid Proteins / Q000276:immunology; D019562:Viral Load; D014765:Viral Vaccines / Q000276:immunology*; D014771:Virion / Q000276:immunology*
D057134:Antibodies, Neutralizing; D019590:Nucleocapsid Proteins; D014765:Viral Vaccines; D007371:Interferon-gamma