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Generation of Escape Variants of Neutralizing Influenza Virus Monoclonal Antibodies

Generation of Escape Variants of Neutralizing Influenza Virus Monoclonal Antibodies

Published on: August 29, 2017

Potente neutralización del Henipavirus por anticuerpos que reconocen diversos sitios en la proteína de unión al

Jinhui Dong¹, Robert W Cross², Michael P Doyle³

¹The Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.

|December 11, 2020

Resumen

Los investigadores descubrieron anticuerpos monoclonales humanos que neutralizan los virus Hendra y Nipah. Estos potentes anticuerpos, HENV-26 y HENV-32, protegieron a los hurones de la letal infección por el virus Nipah, ofreciendo esperanzas para nuevos tratamientos y desarrollo de vacunas.

Área de la Ciencia:

Virología
Inmunología
Biología estructural

Sus antecedentes:

El virus Hendra (HeV) y el virus Nipah (NiV) son virus zoonóticos emergentes altamente patógenos.
Los henipavirus causan enfermedades respiratorias y neurológicas graves con altas tasas de mortalidad en humanos.

Objetivo del estudio:

Identificar y caracterizar los anticuerpos monoclonales humanos de origen natural (mAbs) dirigidos a la proteína de unión al receptor de HeV (RBP).
Evaluar la capacidad de neutralización y la eficacia protectora de estos mAbs contra las infecciones por HeV y NiV.

Principales métodos:

Aislamiento y caracterización de las mAbs humanas contra el HeV-RBP.
Pruebas de neutralización viral y experimentos de clasificación de epítopos.
Análisis estructural de los complejos mAb-RBP mediante cristalografía de rayos X.
Estudios de eficacia in vivo en modelos de hurones con infección por NiV.

Principales resultados:

Descubrimiento de mAbs humanos que neutralizan el HeV y algunos que neutralizan el NiV.
Identificación de cinco sitios antigénicos principales en el HeV-RBP.
Demostración de la protección contra la infección letal por NiV en hurones por mAbs HENV-26 y HENV-32.
Conocimientos estructurales sobre la unión de anticuerpos y los mecanismos de inhibición viral.

Conclusiones:

Se han identificado mAbs humanos potentes dirigidos a las vulnerabilidades conservadas en HeV y NiV RBPs.
Estos mAbs son prometedores como agentes profilácticos contra las infecciones por el henipavirus.
Los epítopos identificados son valiosos para el diseño racional de las vacunas de próxima generación.

Palabras clave:

Los linfocitos B El virus de Hendra Infecciones por el Henipavirus El virus Nipah anticuerpos reacciones antígeno-anticuerpo epítopos Estructura molecular de origen monoclonal Profilaxis previa a la exposición Proteína de unión al receptor tratamiento Virales

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