Generation of a live attenuated influenza A vaccine by proteolysis targeting.
Nat Biotechnol
; 40(9): 1370-1377, 2022 09.
Article
en En
| MEDLINE
| ID: mdl-35788567
ABSTRACT
The usefulness of live attenuated virus vaccines has been limited by suboptimal immunogenicity, safety concerns or cumbersome manufacturing processes and techniques. Here we describe the generation of a live attenuated influenza A virus vaccine using proteolysis-targeting chimeric (PROTAC) technology to degrade viral proteins via the endogenous ubiquitin-proteasome system of host cells. We engineered the genome of influenza A viruses in stable cell lines engineered for virus production to introduce a conditionally removable proteasome-targeting domain, generating fully infective PROTAC viruses that were live attenuated by the host protein degradation machinery upon infection. In mouse and ferret models, PROTAC viruses were highly attenuated and able to elicit robust and broad humoral, mucosal and cellular immunity against homologous and heterologous virus challenges. PROTAC-mediated attenuation of viruses may be broadly applicable for generating live attenuated vaccines.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Vacunas contra la Influenza
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Infecciones por Orthomyxoviridae
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Gripe Humana
Límite:
Animals
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Humans
Idioma:
En
Revista:
Nat Biotechnol
Asunto de la revista:
BIOTECNOLOGIA
Año:
2022
Tipo del documento:
Article
País de afiliación:
China