Vaccination with Plasmids Encoding the Fusion Proteins D-S1, D-S1N and O-SN from SARS-CoV-2 Induces an Effective Humoral and Cellular Immune Response in Mice


Por: Mendoza-Ramírez N.J., García-Cordero J., Hernández-Galicia G., Moreno-Licona N.J., Hernandez J., Cabello-Gutierrez C., Zúñiga-Ramos J.A., Morales-Rios E., Pérez-Tapia S.M., Ortiz-Navarrete V., Espinosa-Cantellano M., Fernández-Benavides D.A., Cedillo-Barrón L.

Publicada: 1 ene 2025
Resumen:
Background: Next-generation vaccines against coronavirus disease 2019 (COVID-19) focus on inducing a long-lasting immune response against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and its emerging variants. To achieve this, antigens other than spike proteins have been proposed, and different platforms have been evaluated. Nucleic acid-based vaccines are fundamental for this process. Preclinical data have shown that the SARS-CoV-2 nucleocapsid protein induces a protective cellular immune response, and when combined with the spike protein, the resulting humoral and cellular immune responses are effective against some SARS-CoV-2 variants. Methods: We designed a DNA vaccine against the spike and nucleocapsid proteins of SARS-CoV-2 to generate fusion proteins based on the Delta and Omicron B.5 strains. The most immunogenic regions of the spike and nucleocapsid proteins of the Delta and Omicron B strains were selected using bioinformatics. The nucleotide sequences were cloned into pcDNA3.1, and named pcDNA3.1/D-S1, pcDNA3.1/D-S1N, and pcDNA3.1/O-SN. The immunogenicity of the generated fusion proteins was evaluated by analyzing the humoral and cellular responses elicited after the immunization of BALB/c mice. Results: DNA immunization induced antibody production, neutralization activity, and IFN-? production. The inclusion of the nucleocapsid regions in the plasmid greatly enhanced the immune response. Moreover, cross-reactions with the variants of interest were confirmed. Conclusions: Plasmids-encoding fusion proteins combining the most immunogenic regions of the spike and nucleocapsid proteins present a promising strategy for designing new and effective vaccines against SARS-CoV-2. © 2025 by the authors.

Filiaciones:
Mendoza-Ramírez N.J.:
 Departamento de Biomedicina Molecular CINVESTAV, Av. IPN # 2508 Col, San Pedro Zacatenco, 07360, Mexico

García-Cordero J.:
 Departamento de Biomedicina Molecular CINVESTAV, Av. IPN # 2508 Col, San Pedro Zacatenco, 07360, Mexico

Hernández-Galicia G.:
 Departamento de Biomedicina Molecular CINVESTAV, Av. IPN # 2508 Col, San Pedro Zacatenco, 07360, Mexico

Moreno-Licona N.J.:
 Departamento de Bioquímica Cinvestav, Av. IPN # 2508 Col, San Pedro Zacatenco, 07360, Mexico

Hernandez J.:
 Laboratorio de Inmunología, Centro de Investigación en Alimentación y Desarrollo A. C (CIAD) Carretera a la Victoria, km 0.6, Hermosillo Sonora, 83304, Mexico

Cabello-Gutierrez C.:
 Departamento de Investigación en Virología y Micología, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas (INER), Calzada de Tlalpan 4502Tlalpan, Belisario Domínguez, 14080, Mexico

Zúñiga-Ramos J.A.:
 Departamento de Investigación en Virología y Micología, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas (INER), Calzada de Tlalpan 4502Tlalpan, Belisario Domínguez, 14080, Mexico

 Escuela de Medicina y Ciencias de la Salud, Tecnológico de Monterrey, Monterrey, 64710, Mexico

Morales-Rios E.:
 Departamento de Bioquímica Cinvestav, Av. IPN # 2508 Col, San Pedro Zacatenco, 07360, Mexico

Pérez-Tapia S.M.:
 Unidad de Desarrollo e Investigación en Bioterapéuticos (UDIBI), Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Mexico City, 11340, Mexico

Ortiz-Navarrete V.:
 Departamento de Biomedicina Molecular CINVESTAV, Av. IPN # 2508 Col, San Pedro Zacatenco, 07360, Mexico

Espinosa-Cantellano M.:
 Departamento de Infectómica y Patogénesis Molecular, CINVESTAV, Av. IPN # 2508 Col, San Pedro Zacatenco, 07360, Mexico

Fernández-Benavides D.A.:
 Centro de Ingeniería y Desarrollo Industrial (CIDESI), Av. Playa Pie de la Cuesta No. 702, Desarrollo San Pablo, Querétaro, 76125, Mexico

Cedillo-Barrón L.:
 Departamento de Biomedicina Molecular CINVESTAV, Av. IPN # 2508 Col, San Pedro Zacatenco, 07360, Mexico
ISSN: 2076393X
Editorial
Multidisciplinary Digital Publishing Institute (MDPI), ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND, Suiza
Tipo de documento: Article
Volumen: 13 Número: 2
Páginas:
WOS Id: 001430644900001
ID de PubMed: 40006682
imagen All Open Access; Gold Open Access