<?xml version="1.0" encoding="ISO-8859-1"?><article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance">
<front>
<journal-meta>
<journal-id>2304-0106</journal-id>
<journal-title><![CDATA[Anales de la Academia de Ciencias de Cuba]]></journal-title>
<abbrev-journal-title><![CDATA[Anales de la ACC]]></abbrev-journal-title>
<issn>2304-0106</issn>
<publisher>
<publisher-name><![CDATA[Academia de Ciencias de Cuba]]></publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id>S2304-01062021000200017</article-id>
<title-group>
<article-title xml:lang="es"><![CDATA[Esquemas de inmunización complementaria basados en la combinación de una formulación tetravalente de proteínas recombinantes y virus vivos atenuados: estrategia vacunal contra el dengue]]></article-title>
<article-title xml:lang="en"><![CDATA[Complementary immunization schedules based on combination of a tetravalent formulation of recombinant proteins and attenuated live virus: vaccine strategy against dengue]]></article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Valdés]]></surname>
<given-names><![CDATA[Iris]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Gil]]></surname>
<given-names><![CDATA[Lázaro]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Lazo]]></surname>
<given-names><![CDATA[Laura]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Hermida]]></surname>
<given-names><![CDATA[Lisset]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Guillén]]></surname>
<given-names><![CDATA[Gerardo]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Izquierdo]]></surname>
<given-names><![CDATA[Alienys]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Suzarte]]></surname>
<given-names><![CDATA[Edith]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Cobas]]></surname>
<given-names><![CDATA[Karem]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Guzmán]]></surname>
<given-names><![CDATA[María G]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Thao]]></surname>
<given-names><![CDATA[Phuong]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Anh Duc]]></surname>
<given-names><![CDATA[Hoang]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Yen]]></surname>
<given-names><![CDATA[Phuong]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Duc Loc]]></surname>
<given-names><![CDATA[Hoang]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Trung Dung]]></surname>
<given-names><![CDATA[Le]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Pérez]]></surname>
<given-names><![CDATA[Yusleidi]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Ramírez]]></surname>
<given-names><![CDATA[Rosa]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Álvarez]]></surname>
<given-names><![CDATA[Mayling]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Romero]]></surname>
<given-names><![CDATA[Yaremis]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Yaugel]]></surname>
<given-names><![CDATA[Melyssa]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Marcos]]></surname>
<given-names><![CDATA[Ernesto]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Dat]]></surname>
<given-names><![CDATA[Do Tuan]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Dan Hien]]></surname>
<given-names><![CDATA[Nguyen]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Silva]]></surname>
<given-names><![CDATA[José Ángel]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[González]]></surname>
<given-names><![CDATA[Sonia]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Vázquez]]></surname>
<given-names><![CDATA[Mariela]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Méndez]]></surname>
<given-names><![CDATA[Aina]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Martín]]></surname>
<given-names><![CDATA[Alejandro]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
</contrib-group>
<aff id="Af1">
<institution><![CDATA[,Centro de Ingeniería Genética y Biotecnología  ]]></institution>
<addr-line><![CDATA[ La Habana]]></addr-line>
<country>Cuba</country>
</aff>
<aff id="Af2">
<institution><![CDATA[,Instituto de Medicina Tropical Pedro Kourí  ]]></institution>
<addr-line><![CDATA[ La Habana]]></addr-line>
<country>Cuba</country>
</aff>
<aff id="Af3">
<institution><![CDATA[,Center for Research and Production of Vaccine and Biological  ]]></institution>
<addr-line><![CDATA[ Polyvac]]></addr-line>
<country>Vietnam</country>
</aff>
<aff id="Af4">
<institution><![CDATA[,Company for Vaccines and Biological Products  ]]></institution>
<addr-line><![CDATA[ Vabiotech]]></addr-line>
<country>Vietnam</country>
</aff>
<pub-date pub-type="pub">
<day>00</day>
<month>08</month>
<year>2021</year>
</pub-date>
<pub-date pub-type="epub">
<day>00</day>
<month>08</month>
<year>2021</year>
</pub-date>
<volume>11</volume>
<numero>2</numero>
<copyright-statement/>
<copyright-year/>
<self-uri xlink:href="http://scielo.sld.cu/scielo.php?script=sci_arttext&amp;pid=S2304-01062021000200017&amp;lng=en&amp;nrm=iso"></self-uri><self-uri xlink:href="http://scielo.sld.cu/scielo.php?script=sci_abstract&amp;pid=S2304-01062021000200017&amp;lng=en&amp;nrm=iso"></self-uri><self-uri xlink:href="http://scielo.sld.cu/scielo.php?script=sci_pdf&amp;pid=S2304-01062021000200017&amp;lng=en&amp;nrm=iso"></self-uri><abstract abstract-type="short" xml:lang="es"><p><![CDATA[RESUMEN  Introducción:  El dengue es una de las enfermedades más importantes trasmitida por mosquitos; sin embargo, solo existe una vacuna licenciada, la cual está registrada en 20 países. Sin embargo, la vacuna no podrá ser administrada en niños menores de nueve años de edad, dado el elevado riesgo de hospitalización observado en este grupo etario. Por lo tanto, el desarrollo de nuevos candidatos vacunales y estrategias de inmunización continúan siendo una prioridad para la Organización Mundial de la Salud y la comunidad científica. Objetivos: el presente trabajo describe los resultados obtenidos de la combinación en esquemas complementarios de dos tipos de candidatos vacunales: las proteínas recombinantes y los virus vivos atenuados. En un primer acercamiento, el candidato vacunal tetravalente Tetra DIIIC se administró en primates no humanos previamente infectados con virus dengue. En un segundo estudio se evaluó la combinación de Tetra DIIIC y la formulación tetravalente de virus vivos atenuados por vía molecular TV005, desarrollada por el Instituto de Salud de los Estados Unidos y licenciada a la compañía vietnamita Vabiotech.  Métodos:  Se utilizaron en los estudios primates no humanos sanos de la especie Macaca mulatta. El candidato vacunal tetravalente Tetra DIIIC, consiste en las proteínas recombinantes DIIIC-1-DIIIC4, correspondientes a los cuatro serotipos del virus dengue, adyuvadas en alúmina. La formulación tetravalente de virus vivos atenuados TV005 por Vabiotech incluyó las cepas virales DENV-1 Nauru/74 (WP), DENV-2 Tonga/74, DENV-3 Sleman/78 y DENV-4 Dominica/81.  Resultados:  Los resultados demuestran que la administración de Tetra DIIIC ocho meses después de la infección pudo activar la respuesta específica de las células B y T contra el DENV. Además, se demostró que los animales inoculados con Tetra DIIIC (una o dos dosis) y luego inmunizados con TV005 desarrollan una respuesta de anticuerpos protectora contra los cuatro serotipos del DENV y que la respuesta inmunológica generada por la Tetra DIIIC reduce la viremia LATV significativamente, lo cual pudiera reducir la reactogenicidad que ha afectado a este último durante los ensayos clínicos. Los resultados aquí descritos resaltan la posibilidad de combinar nuestro candidato vacunal Tetra DIIIC con la vacuna tetravalente del virus vivo atenuado en una estrategia reforzada de inmunización. El presente estudio respalda las estrategias reforzadas como alternativa y enfoques promisorios que solucionan los problemas asociados a cada antígeno individual incluido en la combinación.]]></p></abstract>
<abstract abstract-type="short" xml:lang="en"><p><![CDATA[ABSTRACT  Introduction:  Dengue is one of the most important emerging diseases transmitted by mosquitoes; only one vaccine has been approved and licensed in 20 countries against DENV. This vaccine cannot be administered to children younger than 9 years, due to the increased risk of hospitalization observed in this age group. For this reason, the development of new vaccine candidates and/or immunization strategies continue to be a priority to the World Health Organization and the scientific community. Objectives: This work describes the results in prime-boost immunization schedules combining two different vaccine candidates: recombinant proteins and live attenuated vaccines. Firstly, we evaluated the capacity of Tetra DIIIC vaccine candidate to boost a memory immune response generated in DENV-immune monkeys and as a second study, we also evaluated in monkeys the combination of Tetra DIIIC with the LATV vaccine developed by NIAID and licensed to the Vietnamese company Vabiotech under the codename TV005.  Methods: Macaca mulatta non-human primates were used in the studies. The tetravalent vaccine candidate Tetra DIIIC consists of recombinant proteins DIIIC-1-DIIIC4, corresponding to the four dengue virus serotypes, in adjuvant aluminum oxide. Tetravalent formulation of attenuated live viruses TV005 by Vabiotech included the virus strains DENV-1 Nauru/74 (WP), DENV-2 Tonga/74, DENV-3 Sleman/78, and DENV-4 Dominica/81.  Results: Our results demonstrate that administration of Tetra DIIIC eight months after the infection was able to recall DENV specific memory B- and T-cell response. In addition, we demonstrate that animals primed with Tetra DIIIC (one or two doses) and later immunized with TV005 develop a neutralizing, protective antibody response against the four DENV serotypes, and that the immune response generated by Tetra DIIIC reduces LATV viremia significantly, which might reduce the reactogenicity that has afflicted the latter during clinical trials. Results described here highlight the possibility to combine our vaccine candidate Tetra DIIIC with live-attenuated tetravalent vaccine in a prime/boost strategy for immunizations. The present study supports the prime-boost strategies as alternative and promissory approaches solving the troubles associated with each individual antigen included in the combination.]]></p></abstract>
<kwd-group>
<kwd lng="es"><![CDATA[inmunización sensibilización/refuerzo]]></kwd>
<kwd lng="es"><![CDATA[virus dengue]]></kwd>
<kwd lng="es"><![CDATA[proteínas recombinantes]]></kwd>
<kwd lng="es"><![CDATA[virus vivos atenuados]]></kwd>
<kwd lng="es"><![CDATA[anticuerpos]]></kwd>
<kwd lng="es"><![CDATA[respuesta inmunitaria mediada por células]]></kwd>
<kwd lng="en"><![CDATA[prime-boost immunization]]></kwd>
<kwd lng="en"><![CDATA[dengue viruses (DENV)]]></kwd>
<kwd lng="en"><![CDATA[recombinant proteins]]></kwd>
<kwd lng="en"><![CDATA[live-attenuated viruses, antibodies]]></kwd>
<kwd lng="en"><![CDATA[cell-mediated immune response]]></kwd>
</kwd-group>
</article-meta>
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