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Descubrimiento y ingeniería de la respuesta de anticuerpos a un comensal cutáneo prominente

Djenet Bousbaine^1,2, Katherine D Bauman^1,2, Y Erin Chen^1,2

¹Department of Bioengineering, Stanford University, Stanford, CA, USA.

|December 11, 2024

Resumen

El Staphylococcus epidermidis desencadena una fuerte respuesta de anticuerpos. Los investigadores diseñaron esta bacteria común de la piel para crear una vacuna tópica, que ofrece protección contra desafíos letales y posibles nuevas estrategias de vacunación.

Área de la Ciencia:

Inmunología
Microbiología
Vacunas y vacunas

Sus antecedentes:

* *Staphylococcus epidermidis* es una bacteria común de la piel que provoca una respuesta de células T CD8+ incluso sin infección.
* El propósito y el alcance de esta respuesta inmune anticomensal no se comprenden completamente, lo que dificulta las aplicaciones terapéuticas.

Objetivo del estudio:

* Para investigar la respuesta de anticuerpos inducida por la colonización de S. epidermidis.
* Para identificar los objetivos específicos de esta respuesta de anticuerpos.
* Explorar el potencial de redirigir esta respuesta inmune para la vacunación terapéutica.

Principales métodos:

* Se generaron mutantes de la pared celular de S. epidermidis para identificar objetivos de superficie clave.
Se han creado cepas genéticamente modificadas de S. epidermidis que expresan proteínas quiméricas (Aap-TTC, Aap-SpyCatcher).
* Colonización de ratones con S. epidermidis modificado y evaluación de las respuestas de anticuerpos y protección contra desafíos letales.

Principales resultados:

* *S. epidermidis* induce una respuesta de anticuerpos potente, duradera y específica en humanos y primates no humanos.
* La proteína de la superficie celular Aap fue identificada como un objetivo principal de esta respuesta.
La S. epidermidis modificada produjo anticuerpos neutralizantes y protegió a los ratones contra el reto letal.
* La conjugación con inmunógenos a través de Aap-SpyCatcher indujo altos títulos de anticuerpos, incluida la IgA mucosal.

Conclusiones:

* La inmunidad a *S. epidermidis* implica una respuesta coordinada de las células T y B.
* La respuesta de los anticuerpos puede ser redirigida contra los patógenos utilizando comensales modificados.
* Este enfoque ofrece una nueva estrategia para la vacunación tópica.

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