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Las exposiciones repetidas a Omicron anulan la impresión inmune ancestral del SARS-CoV-2

Ayijiang Yisimayi^1,2, Weiliang Song^1,2, Jing Wang^1,2

¹Biomedical Pioneering Innovation Center (BIOPIC), School of Life Sciences, Peking University, Beijing, P. R. China.

|November 22, 2023

Resumen

La estimulación repetida de Omicron puede superar la impresión inmune ancestral de la vacuna COVID-19, mejorando las respuestas de anticuerpos. Se recomienda abandonar la cepa ancestral en las vacunas y usar refuerzos Omicron duales para una mejor protección contra las variantes del SARS-CoV-2.

Área de la Ciencia:

Virología
Inmunología
Vacunas y vacunas

Sus antecedentes:

Las variantes emergentes del SARS-CoV-2 requieren composiciones de vacunas COVID-19 actualizadas.
La vacunación basada en la cepa ancestral puede inducir la impresión inmune, comprometiendo las respuestas a los refuerzos basados en Omicron.
Las estrategias para contrarrestar la impresión inmune son cruciales para una vacunación efectiva contra el COVID-19.

Objetivo del estudio:

Investigar el grado y la dinámica de la impresión inmune en respuesta a las variantes del SARS-CoV-2.
Evaluar el impacto de la estimulación Omicron repetida en la impresión inmune en modelos de ratón y cohortes humanas.
Identificar estrategias para mitigar la impresión inmune y mejorar la eficacia de la vacuna contra las variantes actuales.

Principales métodos:

Estudios realizados en modelos de ratón y cohortes humanas.
Análisis de las respuestas de anticuerpos tras la estimulación única y repetida con Omicron.
Escaneo mutacional profundo de epítopos del dominio de unión al receptor (RBD) para anticuerpos monoclonales.
Caracterización de la evolución de la variante SARS-CoV-2, incluidos los puntos de acceso XBB.1.5 RBD.

Principales resultados:

La estimulación Omicron repetida, particularmente un segundo refuerzo, mitigó la impresión inmune inducida por la cepa ancestral en ratones y humanos.
La doble exposición a Omicron generó amplias respuestas de neutralización en el plasma y la mucosa nasal, induciendo anticuerpos específicos de Omicron con epítopos distintos de RBD.
Se identificaron puntos calientes de evolución de XBB.1.5 RBD que mejoran la evasión inmune mientras se mantiene la unión ACE2.
Se recomienda el abandono del componente WT en las vacunas y los refuerzos duales de Omicron para personas sin exposición previa a Omicron.

Conclusiones:

La estimulación repetida de Omicron supera efectivamente la impresión inmune ancestral inducida por la vacuna COVID-19.
Las estrategias de vacunación deben dar prioridad a los antígenos específicos de Omicron, potencialmente a través de un doble refuerzo, para mejorar la protección contra las variantes del SARS-CoV-2.
Se sugiere abandonar la cepa ancestral en las vacunas COVID-19 actualizadas para mejorar la eficacia.

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