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Una vacuna con ácido siálico fluorado contra la meningitis B y C

Christina Jordan¹, Kathrin Siebold¹, Patricia Priegue^2,3

¹Institute for Organic Chemistry, University of Münster, Corrensstraße 36, Münster 48149, Germany.

Journal of the American Chemical Society

|May 20, 2024

Resumen

Un nuevo plomo de vacuna de disacáridos fluorados es prometedor contra los serogrupos C y B de Neisseria meningitidis. Este antígeno sintético produce anticuerpos protectores, allanando el camino para nuevas vacunas contra la meningitis.

Área de la Ciencia:

* Química sintética y inmunología.
* Desarrollo de vacunas y glucobiología.

Sus antecedentes:

* Los polisacáridos capsulares bacterianos (CPS) contienen epítopos α- 2,9) -sialílicos específicos que son cruciales para la patogénesis de la Neisseria meningitidis.
* La incorporación de flúor en el descubrimiento de fármacos ofrece beneficios, incluida una mejor selectividad y estabilidad.

Objetivo del estudio:

* Desarrollar una vacuna sintética dirigida a los serogrupos C y B de Neisseria meningitidis.
* Para evaluar la inmunogenicidad y la eficacia protectora de una vacuna conjugada de disialosido fluorado.

Principales métodos:

* Síntesis de un bioisóster disialosídico doblemente fluorado.
* Conjugación del disialosido con proteínas portadoras (CRM197 y PorA) para crear vacunas semisintéticas.
* Inmunización de ratones y evaluación de las respuestas de anticuerpos (IgG), la especificidad del glicano y la protección funcional mediante ensayos bactericidas séricos (SBA) y de eliminación opsonofagocítica (OPKA).

Principales resultados:

* Las vacunas conjugadas de disialosido fluorado indujeron respuestas estables de IgG a largo plazo en ratones.
* Los anticuerpos generados demostraron una alta especificidad para el epitopo nativo de CPS y proporcionaron protección contra la infección por MenC y/ o MenB in vitro.
* Se creó con éxito una vacuna bivalente que combina los componentes MenC y MenB.

Conclusiones:

* El disialosido sintético fluorado es un antígeno potente para las vacunas de Neisseria meningitidis.
* Este enfoque ofrece una estrategia prometedora para desarrollar vacunas efectivas contra múltiples serogrupos meningocócicos.
* El estudio pone de relieve el potencial de la modificación de bioisósteros en el diseño de vacunas.

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