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Amplificación de la infección dependiente de anticuerpos en la inmunopatogénesis del dengue grave, implicaciones para el desarrollo y uso de las vacunas
Antibody-dependent enhancement in the immunopathogenesis of severe dengue, implications for the development and use of vaccines
DOI:
https://doi.org/10.15446/abc.v24n3.79410Palabras clave:
Anticuerpos, dengue grave, inmunomodulación, patogénesis, vacuna (es)Antibodies, immunomodulation, pathogenesis, severe dengue, vaccine (en)
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Actualmente, la infección por el virus de dengue (DENV) es uno de los problemas más importantes de salud pública en países tropicales y endémicos como Colombia, pues en tanto puede ser producida por cuatro diferentes serotipos virales, durante las infecciones secundarias se presentan frecuentemente cuadros más severos que incluso pueden llevar a desenlaces fatales. El centro de la fisiopatología del dengue grave es el daño producido al endotelio, que se traduce en un aumento en la permeabilidad vascular que se evidencia como fuga plasmática, descontrol en la coagulación y daño de órganos. Aunque hay varias teorías que explican la enfermedad severa, el fenómeno denominado amplificación de la infección dependiente de anticuerpos (antibody dependent enhancement, ADE) es el más conocido. En este, se postula que el virus causante de una infección secundaria es reconocido, pero no neutralizado, por anticuerpos generados en la infección previa e internalizado en las células susceptibles usando receptores Fc-gamma, lo cual aumenta la replicación viral e induce modificaciones en la respuesta inmune celular que contribuyen al desarrollo de dengue grave. En este escrito, se realiza una revisión de los hallazgos sobre los mecanismos involucrados en el fenómeno de ADE y cómo pueden contribuir a la progresión hacia dengue grave, describiendo los conceptos de ADE extrínseco e intrínseco, además de como este fenómeno debe ser tenido en cuenta para el diseño, desarrollo e implementación de una vacuna para dengue, en tanto es capaz de afectar su eficacia y seguridad.
Dengue virus infection is the most important vector transmitted disease in tropical countries such as Colombia, where all the four dengue virus serotypes are circulating and are involved in successive secondary infections which induce severe or even fatal cases. The central key to understanding the severe dengue cases is the endothelial function damage which appears as plasma leakage, coagulation impairment, and organ compromise. Severe dengue could be explained by different theories, among them the antibodydependent enhancement (ADE) phenomenon is the best known. This theory postulates that the second heterotypic virus causing a secondary infection is recognized by antibodies raised during the first infection but are ineffective to neutralize the virus. Instead this virus-antibody complex is internalized by Fc-gamma receptor-bearing cells increasing the viral replication and inducing an aberrant immune response that contributes to severe dengue presentation. This manuscript is aimed to review the evidence about the ADE phenomenon and its involvement in the severe evolution of dengue cases. Here, it will be described the extrinsic and intrinsic ADE concepts and how these phenomena must be considered to the design, development, and implementation of a dengue vaccine because the evidence indicates that ADE affects both efficacy and safety of vaccine prototypes.
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