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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-\u03b3\u2013secreting 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.<\/jats:p>","DOI":"10.4049\/jimmunol.1600927","type":"journal-article","created":{"date-parts":[[2016,9,29]],"date-time":"2016-09-29T02:29:09Z","timestamp":1475116149000},"page":"3597-3606","source":"Crossref","is-referenced-by-count":30,"title":["A Tetravalent Formulation Based on Recombinant Nucleocapsid-like Particles from Dengue Viruses Induces a Functional Immune Response in Mice and Monkeys"],"prefix":"10.1093","volume":"197","author":[{"given":"L\u00e1zaro","family":"Gil","sequence":"first","affiliation":[{"name":"Center for Genetic Engineering and Biotechnology , Havana 10 600,","place":["Cuba"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karem","family":"Cobas","sequence":"additional","affiliation":[{"name":"Center for Genetic Engineering and Biotechnology , Havana 10 600,","place":["Cuba"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Lazo","sequence":"additional","affiliation":[{"name":"Center for Genetic Engineering and Biotechnology , Havana 10 600,","place":["Cuba"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernesto","family":"Marcos","sequence":"additional","affiliation":[{"name":"Center for Genetic Engineering and Biotechnology , Havana 10 600,","place":["Cuba"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Center for Genetic Engineering and Biotechnology , Havana 10 600,","place":["Cuba"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edith","family":"Suzarte","sequence":"additional","affiliation":[{"name":"Center for Genetic Engineering and Biotechnology , Havana 10 600,","place":["Cuba"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alienys","family":"Izquierdo","sequence":"additional","affiliation":[{"name":"Pan American Health Organization\/World Health Organization Collaborating Center for the Study of Dengue and Its Vector, Department of Virology, Pedro Kour\u00ed Tropical Medicine Institute , Havana 17 100,","place":["Cuba"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iris","family":"Vald\u00e9s","sequence":"additional","affiliation":[{"name":"Center for Genetic Engineering and Biotechnology , Havana 10 600,","place":["Cuba"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aracelys","family":"Blanco","sequence":"additional","affiliation":[{"name":"Center for Genetic Engineering and Biotechnology , Havana 10 600,","place":["Cuba"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro","family":"Puentes","sequence":"additional","affiliation":[{"name":"Center for Genetic Engineering and Biotechnology , Havana 10 600,","place":["Cuba"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaremis","family":"Romero","sequence":"additional","affiliation":[{"name":"Center for Genetic Engineering and Biotechnology , Havana 10 600,","place":["Cuba"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusleidi","family":"P\u00e9rez","sequence":"additional","affiliation":[{"name":"Center for Genetic Engineering and Biotechnology , Havana 10 600,","place":["Cuba"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda G","family":"Guzm\u00e1n","sequence":"additional","affiliation":[{"name":"Pan American Health Organization\/World Health Organization Collaborating Center for the Study of Dengue and Its Vector, Department of Virology, Pedro Kour\u00ed Tropical Medicine Institute , Havana 17 100,","place":["Cuba"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3098-0970","authenticated-orcid":false,"given":"Gerardo","family":"Guill\u00e9n","sequence":"additional","affiliation":[{"name":"Center for Genetic Engineering and Biotechnology , Havana 10 600,","place":["Cuba"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisset","family":"Hermida","sequence":"additional","affiliation":[{"name":"Center for Genetic Engineering and Biotechnology , Havana 10 600,","place":["Cuba"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2016,11,1]]},"reference":[{"key":"2025030617583681000_r1","doi-asserted-by":"crossref","first-page":"1445","DOI":"10.1007\/s00705-013-1645-3","article-title":"Secondary infection as a risk factor for dengue hemorrhagic fever\/dengue shock syndrome: an historical perspective and role of antibody-dependent enhancement of infection","volume":"158","author":"Guzman","year":"2013","journal-title":"Arch. 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