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Bases estructurales para la evasión continua de anticuerpos por el dominio de unión al receptor del SARS-CoV-2
Katherine G Nabel1, Sarah A Clark1, Sundaresh Shankar1
1Department of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.
Science (New York, N.Y.)
|December 2, 2021
Resumen
El virus SARS-CoV-2 evoluciona rápidamente, desarrollando múltiples mutaciones en su dominio de unión al receptor (RBD) para evadir los anticuerpos. Esta adaptación viral plantea desafíos para las terapias y vacunas de anticuerpos actuales, lo que pone de relieve la necesidad de una investigación en curso.
Área de la Ciencia:
- Virología e Inmunología
- Biología molecular
- Enfermedades infecciosas
Sus antecedentes:
- Las investigaciones anteriores se centraron en las variantes de SARS-CoV-2 con menos mutaciones.
- Comprender la resistencia a la neutralización de anticuerpos es crucial para el desarrollo terapéutico.
- El surgimiento de las variantes del SARS-CoV-2 requiere evaluar la evolución viral adicional.
Objetivo del estudio:
- Investigar el impacto de las mutaciones extensas en la neutralización del SARS-CoV-2.
- Para explorar los mecanismos de escape de anticuerpos en variantes virales avanzadas.
- Evaluar la eficacia de las terapias de anticuerpos existentes contra las cepas de SARS-CoV-2 en evolución.
Principales métodos:
- Construcción y análisis de pseudotipos de SARS-CoV-2 con hasta siete mutaciones de RBD.
- Evaluación de la resistencia a la neutralización utilizando anticuerpos terapéuticos y suero de personas vacunadas.
- Identificación de sitios específicos de unión de anticuerpos y mecanismos de escape viral, incluida la adquisición de glicano ligado a N.
Principales resultados:
- Los pseudotipos con numerosas mutaciones simultáneas de RBD exhiben una mayor resistencia a la neutralización.
- Las variantes avanzadas muestran una mayor evasión de anticuerpos terapéuticos y inmunidad inducida por la vacuna.
- Un anticuerpo específico dirigido al núcleo RBD puede neutralizar las variantes probadas, pero la adquisición de glicano ligado a N confiere escape.
Conclusiones:
- El dominio de unión al receptor del SARS-CoV-2 puede acomodar múltiples mutaciones de escape de anticuerpos, lo que facilita la evolución viral.
- Las variantes emergentes del SARS-CoV-2 representan una amenaza significativa para la efectividad de las actuales intervenciones basadas en anticuerpos.
- La adaptación continua del SARS-CoV-2 sugiere desafíos continuos en el control de la pandemia y requiere el desarrollo de anticuerpos ampliamente neutralizantes.
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