<?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>S2304-01062023000400022</article-id>
<title-group>
<article-title xml:lang="es"><![CDATA[Evaluación preclínica y clínica de SOBERANA® 01. Candidato vacunal contra la COVID-19]]></article-title>
<article-title xml:lang="en"><![CDATA[Preclinical and clinical evaluation of SOBERANA® 01. Vaccine candidate against COVID-19]]></article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Climent Ruiz]]></surname>
<given-names><![CDATA[Yanet]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Santana Mederos]]></surname>
<given-names><![CDATA[Darielys]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[PérezRodríguez]]></surname>
<given-names><![CDATA[Sonia]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Rodríguez González]]></surname>
<given-names><![CDATA[Meiby de la Caridad]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[García Rivera]]></surname>
<given-names><![CDATA[Dagmar]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Sánchez Ramírez]]></surname>
<given-names><![CDATA[Belinda]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Valdés Balbín]]></surname>
<given-names><![CDATA[Yury]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Vérez Bencomo]]></surname>
<given-names><![CDATA[Vicente]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Rodríguez Noda]]></surname>
<given-names><![CDATA[Laura M.]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Pérez Nicado]]></surname>
<given-names><![CDATA[Rocmira]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Ochoa Azze]]></surname>
<given-names><![CDATA[Rolando]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Boggiano Ayo]]></surname>
<given-names><![CDATA[Tammy]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Valenzuela Silva]]></surname>
<given-names><![CDATA[Carmen María]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
<xref ref-type="aff" rid="Aaf"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[González Rodríguez]]></surname>
<given-names><![CDATA[Humberto]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Ramírez González]]></surname>
<given-names><![CDATA[Ubel J.]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Paredes Moreno]]></surname>
<given-names><![CDATA[Beatriz]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[García Rivera]]></surname>
<given-names><![CDATA[Daniel]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Labrada Regalado]]></surname>
<given-names><![CDATA[Claudia]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Hernández García]]></surname>
<given-names><![CDATA[Tays]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Noa Romero]]></surname>
<given-names><![CDATA[Enrique]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Díaz Hernández]]></surname>
<given-names><![CDATA[Marianniz]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[OrosaVázquez]]></surname>
<given-names><![CDATA[Ivette]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[BergadoBáez]]></surname>
<given-names><![CDATA[Gretchen]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Pi Estopiñán]]></surname>
<given-names><![CDATA[Franciscary]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Hernández Salazar]]></surname>
<given-names><![CDATA[Tamara]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Fariñas Medina]]></surname>
<given-names><![CDATA[Mildrey]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Enriquez Puertas]]></surname>
<given-names><![CDATA[Juliet María]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[González Sosa]]></surname>
<given-names><![CDATA[Nibaldo Luis]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[González Delgado]]></surname>
<given-names><![CDATA[Carlos A.]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Rubino Moreno]]></surname>
<given-names><![CDATA[Jorman]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Díaz Machado]]></surname>
<given-names><![CDATA[Alina]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[González Freire]]></surname>
<given-names><![CDATA[Yunior]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Esmoris Mena]]></surname>
<given-names><![CDATA[Yudisleidy]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Rosales Gil]]></surname>
<given-names><![CDATA[Lilia Beatríz]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Chappi Estévez]]></surname>
<given-names><![CDATA[Yanet]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Amoroto Roig]]></surname>
<given-names><![CDATA[Mayté]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Martínez Pérez]]></surname>
<given-names><![CDATA[Marisel]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Ontiveiro Pino]]></surname>
<given-names><![CDATA[Ivis]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Landys Chovel Cuervo]]></surname>
<given-names><![CDATA[Mario]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Garrido Arteaga]]></surname>
<given-names><![CDATA[Raine]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Cardoso San Jorge]]></surname>
<given-names><![CDATA[Félix]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[González Mugica Romero]]></surname>
<given-names><![CDATA[Raúl]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Fernández Castillo]]></surname>
<given-names><![CDATA[Sonsire]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Ojito Magaz]]></surname>
<given-names><![CDATA[Eduardo]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Chiodo]]></surname>
<given-names><![CDATA[Fabrizio]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
<xref ref-type="aff" rid="Aaf"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Paquet]]></surname>
<given-names><![CDATA[Francoise]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Fang]]></surname>
<given-names><![CDATA[Cheng]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Guang-Wu]]></surname>
<given-names><![CDATA[Chen]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
</contrib-group>
<aff id="Af1">
<institution><![CDATA[,Instituto Finlay de Vacunas  ]]></institution>
<addr-line><![CDATA[La Habana ]]></addr-line>
<country>Cuba</country>
</aff>
<aff id="Af2">
<institution><![CDATA[,Centro de Inmunología Molecular  ]]></institution>
<addr-line><![CDATA[La Habana ]]></addr-line>
<country>Cuba</country>
</aff>
<aff id="Af3">
<institution><![CDATA[,Centro Nacional de Toxicología  ]]></institution>
<addr-line><![CDATA[La Habana ]]></addr-line>
<country>Cuba</country>
</aff>
<aff id="Af4">
<institution><![CDATA[,Universidad de La Habana Facultad de Química ]]></institution>
<addr-line><![CDATA[La Habana ]]></addr-line>
<country>Cuba</country>
</aff>
<aff id="Af5">
<institution><![CDATA[,Universidad de La Habana Instituto de Cibernética, Matemática y Física ]]></institution>
<addr-line><![CDATA[La Habana ]]></addr-line>
<country>Cuba</country>
</aff>
<aff id="Af6">
<institution><![CDATA[,Centro de Investigaciones de la Defensa Civil  ]]></institution>
<addr-line><![CDATA[La Habana ]]></addr-line>
<country>Cuba</country>
</aff>
<aff id="Af7">
<institution><![CDATA[,Centro Nacional Coordinador de Ensayos Clínicos  ]]></institution>
<addr-line><![CDATA[La Habana ]]></addr-line>
<country>Cuba</country>
</aff>
<aff id="Af8">
<institution><![CDATA[,Universidad Libre de Amsterdam Centros Médicos de la Universidad de Amsterdam ]]></institution>
<addr-line><![CDATA[Amsterdam ]]></addr-line>
<country>Netherlands</country>
</aff>
<aff id="Af9">
<institution><![CDATA[,Consejo Nacional de Investigación Instituto de Química Biomolecular ]]></institution>
<addr-line><![CDATA[Nápoles ]]></addr-line>
<country>Italia</country>
</aff>
<aff id="A10">
<institution><![CDATA[,Centro de Biofísica Molecular  ]]></institution>
<addr-line><![CDATA[Orleans ]]></addr-line>
<country>Francia</country>
</aff>
<aff id="A11">
<institution><![CDATA[,Chengdu Olisynn Biotech  ]]></institution>
<addr-line><![CDATA[Chengdou ]]></addr-line>
<country>China</country>
</aff>
<aff id="A12">
<institution><![CDATA[,Shanghai Fenglin Glycodrug Promotion Center  ]]></institution>
<addr-line><![CDATA[Shanghai ]]></addr-line>
<country>China</country>
</aff>
<pub-date pub-type="pub">
<day>00</day>
<month>12</month>
<year>2023</year>
</pub-date>
<pub-date pub-type="epub">
<day>00</day>
<month>12</month>
<year>2023</year>
</pub-date>
<volume>13</volume>
<numero>4</numero>
<copyright-statement/>
<copyright-year/>
<self-uri xlink:href="http://scielo.sld.cu/scielo.php?script=sci_arttext&amp;pid=S2304-01062023000400022&amp;lng=en&amp;nrm=iso"></self-uri><self-uri xlink:href="http://scielo.sld.cu/scielo.php?script=sci_abstract&amp;pid=S2304-01062023000400022&amp;lng=en&amp;nrm=iso"></self-uri><self-uri xlink:href="http://scielo.sld.cu/scielo.php?script=sci_pdf&amp;pid=S2304-01062023000400022&amp;lng=en&amp;nrm=iso"></self-uri><abstract abstract-type="short" xml:lang="es"><p><![CDATA[RESUMEN  Introducción:  SOBERANA® 01 se desarrolló en el Instituto Finlay de Vacunas para el enfrentamiento a la epidemia causada por el virus SARS-CoV-2. Este candidato se basa en el dominio de unión al receptor en forma dimérica, combinado con vesículas purificadas de membrana externa de meningococo del serogrupo B como inmunopotenciador de la respuesta inmune adsorbidos en hidróxido de aluminio.  Métodos:  Se diseñó el antígeno con la peculiaridad de tener una cisteína libre en la posición 538, que permite la formación de dímeros del dominio de unión al receptor. En estudios preclínicos se evaluó la inmunogenicidad del dímero combinado con las vesículas de membrana externa y se realizaron estudios toxicológicos. Además, se diseñó un estudio clínico fase I en sujetos de 19 años a 59 años.  Resultados:  La presentación antigénica en forma de dímero combinado con las vesículas demostró ser segura e inmunogénica en modelos animales observando un incremento significativo de la respuesta inmune cuando se compara con la forma monomérica. Durante la evaluación clínica fase I, que incluyeron sujetos aparentemente sanos de entre 19 años y 59 años de edad, se demostró que SOBERANA® 01 conduce a un aumento importante en la respuesta de anticuerpos neutralizantes en comparación con el uso de hidróxido de aluminio como único adyuvante. Después de la tercera dosis, el 100 % de los sujetos seroconvirtieron en el grupo inmunizado con SOBERANA® 01. Conclusiones: Se demostró la inmunogenicidad y la capacidad neutralizante de los anticuerpos inducidos por SOBERANA® 01. El análisis de los sueros de las personas vacunadas demostró que la formulación que contiene las vesículas de membrana externa provoca un efecto neutralizante más potente contra varios mutantes del dominio de unión al receptor presentes en los COV, incluidos los mutantes triples del dominio de unión al receptor de la variante Beta.]]></p></abstract>
<abstract abstract-type="short" xml:lang="en"><p><![CDATA[ABSTRACT  Introduction:  SOBERANA® 01 was developed at the Finlay Vaccine Institute to combat the epidemic caused by the SARS-CoV-2 virus. This candidate is based on the Receptor Binding Domain (RBD) in dimeric form combined with purified vesicles from outer membrane of serogroup B meningococcus as immunopotentiator of the immune response adsorbed on aluminum hydroxide.  Methods:  The antigen was designed with the peculiarity of having a free cysteine at position 538, which allows the formation of RBD dimers. In preclinical studies it was evaluated the immunogenicity of the dimer combined with the outer membrane vesicles and they were performed toxicological studies. In addition, it was designed a Phase I clinical study in subjects from 19 to 59 years old.  Results:  The antigenic presentation in the form of dimer combined with the vesicles proved to be safe and immunogenic in animal models, observing a significant increase in the immune response when compared to the monomeric form. During the Phase I clinical evaluation, which included apparently healthy subjects between the ages of 19 and 59, it was demonstrated that SOBERANA® 01 lead to a significant increase in the neutralizing antibody response compared to the use of aluminum hydroxide as the sole adjuvant. After the third dose, 100% of the subjects seroconverted to the group immunized with SOBERANA® 01. Conclusions: It was demonstrated the immunogenicity and neutralizing capacity of the antibodies induced by SOBERANA® 01. The analysis of the sera of the vaccinated persons demonstrated that the formulation containing the OMVs causes a more potent neutralizing effect against several RBD mutants present in VOCs, including the RBD triple mutants of the beta variant.]]></p></abstract>
<kwd-group>
<kwd lng="es"><![CDATA[COVID-19]]></kwd>
<kwd lng="es"><![CDATA[SARS-CoV-2]]></kwd>
<kwd lng="es"><![CDATA[vacunas]]></kwd>
<kwd lng="es"><![CDATA[anticuerpos neutralizantes]]></kwd>
<kwd lng="en"><![CDATA[COVID-19]]></kwd>
<kwd lng="en"><![CDATA[SARS-CoV-2]]></kwd>
<kwd lng="en"><![CDATA[Vaccine]]></kwd>
<kwd lng="en"><![CDATA[Neutralizing antibodies]]></kwd>
</kwd-group>
</article-meta>
</front><back>
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<article-title xml:lang=""><![CDATA[Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARSCoV-2: a preliminary report of a phase 1/2, single-blind, randomized controlled trial]]></article-title>
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