SARS-CoV-2-derived RNA replicons as safe and effective vaccines

A collection of RNA replicons (RRs) derived from severe acute respiratory syndrome 2 (SARS-CoV-2) for use in vaccine design was constructed by genetic engineering using bacterial artificial chromosomes. A replicon, which was deleted in six genes (3a, 3c, E, 6, 7a, and 7b) was selected. Cells infecte...

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Detalles Bibliográficos
Autores: Villarejo-Torres, Marta, Nombela, Iván, Muñoz-Santos, Diego, Ruiz-Yuste, Mercedes, Marchena-Pasero, Ana, Rueda-Huélamo, María, Ripoll-Gómez, Jorge, Sánchez-Cordón, Pedro J., Fernández del Ama, Laura, Honrubia, José M., Gutiérrez Álvarez, Javier, Hurtado Tamayo, Jesús, Requena-Platek, Ricardo, Guzmán, María, Casasnovas, José María, García-Arriaza, Juan, Pérez, Patricia, Martín-Jouve, Beatriz, Matamoros Grande, Tania, Pintado, Belén, Perlman, Stanley, Solá Gurpegui, Isabel, Zúñiga Lucas, Sonia, Enjuanes Sánchez, Luis
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/401713
Acceso en línea:http://hdl.handle.net/10261/401713
https://api.elsevier.com/content/abstract/scopus_id/105016909298
Access Level:acceso abierto
Palabra clave:RNA replicon
SARS-CoV-2
Coronavirus
Vaccine
Descripción
Sumario:A collection of RNA replicons (RRs) derived from severe acute respiratory syndrome 2 (SARS-CoV-2) for use in vaccine design was constructed by genetic engineering using bacterial artificial chromosomes. A replicon, which was deleted in six genes (3a, 3c, E, 6, 7a, and 7b) was selected. Cells infected with the RR vaccine candidate led to the formation of virus-like particles that, due to the failure of being secreted, increase vaccine safety, in contrast to the wild type virions. The replicon maintained the production of RNAs encoding at least proteins S, M, and N for several days. Intranasal immunization with the RR of transgenic mice, expressing human ACE2, elicited respiratory mucosal immunity. Immunization protected against challenge with SARS-CoV-2, inducing IgG, IgM, and IgA antibodies to the spike (S) protein, the receptor binding domain, N and M proteins, and cellular immune responses (CD4+, CD8+, and long-term memory T cells). Coinfection of cells with the RR vaccine and a full-length SARS-CoV-2 led to a significant inhibition of replication of full-length virus, increasing the safety of the RR vaccine. The RR vaccine induced a minor inflammatory reaction in the absence of major side effects and was stable at different temperatures. An updated RR expressing XBB.1.5 S protein elicited neutralizing antibodies against the homologous virus and provided full protection against recent SARS-CoV-2 variants.

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