Caveats of chimpanzee ChAdOx1 adenovirus-vectored vaccines to boost anti-SARS-CoV-2 protective immunity in mice


Por: Cervantes-Torres J., Cabello-Gutiérrez C., Ayón-Núñez D.-A., Soldevila G., Olguin-Alor R., Diaz G., Acero G., Segura-Velázquez R., Huerta L., Gracia-Mora I., Cobos L., Pérez-Tapia M., Almagro J.C., Suárez-Güemes F., Bobes R.J., Fragoso G., Sciutto E., Laclette J.P.

Publicada: 1 ene 2024
Resumen:
Abstract: Several COVID-19 vaccines use adenovirus vectors to deliver the SARS-CoV-2 spike (S) protein. Immunization with these vaccines promotes immunity against the S protein, but against also the adenovirus itself. This could interfere with the entry of the vaccine into the cell, reducing its efficacy. Herein, we evaluate the efficiency of an adenovirus-vectored vaccine (chimpanzee ChAdOx1 adenovirus, AZD1222) in boosting the specific immunity compared to that induced by a recombinant receptor-binding domain (RBD)-based vaccine without viral vector. Mice immunized with the AZD1222 human vaccine were given a booster 6 months later, with either the homologous vaccine or a recombinant vaccine based on RBD of the delta variant, which was prevalent at the start of this study. A significant increase in anti-RBD antibody levels was observed in rRBD-boosted mice (31–61%) compared to those receiving two doses of AZD1222 (0%). Significantly higher rates of PepMix™- or RBD-elicited proliferation were also observed in IFN?-producing CD4 and CD8 cells from mice boosted with one or two doses of RBD, respectively. The lower efficiency of the ChAdOx1-S vaccine in boosting specific immunity could be the result of a pre-existing anti-vector immunity, induced by increased levels of anti-adenovirus antibodies found both in mice and humans. Taken together, these results point to the importance of avoiding the recurrent use of the same adenovirus vector in individuals with immunity and memory against them. It also illustrates the disadvantages of ChAdOx1 adenovirus-vectored vaccine with respect to recombinant protein vaccines, which can be used without restriction in vaccine-booster programs. Key points: • ChAdOx1 adenovirus vaccine (AZD1222) may not be effective in boosting anti-SARS-CoV-2 immunity • A recombinant RBD protein vaccine is effective in boosting anti-SARS-CoV-2 immunity in mice • Antibodies elicited by the rRBD-delta vaccine persisted for up to 3 months in mice © 2024, The Author(s).

Filiaciones:
Cervantes-Torres J.:
 School of Veterinary Medicine, Universidad Nacional Autónoma de México, Coyoacán, Mexico City, 04510, Mexico

 Biomedical Research Institute, Universidad Nacional Autónoma de México, Coyoacán, Mexico City, 04510, Mexico

Cabello-Gutiérrez C.:
 Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Calzada de Tlalpan 4502, Belisario Domínguez Secc. 16, Tlalpan, CDMX, Mexico City, 14080, Mexico

Ayón-Núñez D.-A.:
 School of Veterinary Medicine, Universidad Nacional Autónoma de México, Coyoacán, Mexico City, 04510, Mexico

Soldevila G.:
 Biomedical Research Institute, Universidad Nacional Autónoma de México, Coyoacán, Mexico City, 04510, Mexico

 Laboratorio Nacional de Citometría de Flujo, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Coyoacán, Mexico City, 04510, Mexico

Olguin-Alor R.:
 Biomedical Research Institute, Universidad Nacional Autónoma de México, Coyoacán, Mexico City, 04510, Mexico

 Laboratorio Nacional de Citometría de Flujo, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Coyoacán, Mexico City, 04510, Mexico

Diaz G.:
 Biomedical Research Institute, Universidad Nacional Autónoma de México, Coyoacán, Mexico City, 04510, Mexico

Acero G.:
 Biomedical Research Institute, Universidad Nacional Autónoma de México, Coyoacán, Mexico City, 04510, Mexico

Segura-Velázquez R.:
 School of Veterinary Medicine, Universidad Nacional Autónoma de México, Coyoacán, Mexico City, 04510, Mexico

Huerta L.:
 Biomedical Research Institute, Universidad Nacional Autónoma de México, Coyoacán, Mexico City, 04510, Mexico

Gracia-Mora I.:
 Unidad de Experimentación Preclínica, Facultad de Química, Universidad Nacional Autónoma de México, Coyoacán, Mexico City, 04510, Mexico

Cobos L.:
 School of Veterinary Medicine, Universidad Nacional Autónoma de México, Coyoacán, Mexico City, 04510, Mexico

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

Almagro J.C.:
 Unidad de Desarrollo e Investigación en Bioterapéuticos (UDIBI), Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Mexico City, 11340, Mexico

Suárez-Güemes F.:
 School of Veterinary Medicine, Universidad Nacional Autónoma de México, Coyoacán, Mexico City, 04510, Mexico

Bobes R.J.:
 Biomedical Research Institute, Universidad Nacional Autónoma de México, Coyoacán, Mexico City, 04510, Mexico

Fragoso G.:
 Biomedical Research Institute, Universidad Nacional Autónoma de México, Coyoacán, Mexico City, 04510, Mexico

Sciutto E.:
 Biomedical Research Institute, Universidad Nacional Autónoma de México, Coyoacán, Mexico City, 04510, Mexico

Laclette J.P.:
 Biomedical Research Institute, Universidad Nacional Autónoma de México, Coyoacán, Mexico City, 04510, Mexico
ISSN: 01757598
Editorial
SPRINGER, 233 SPRING ST, NEW YORK, NY 10013 USA, Estados Unidos America
Tipo de documento: Article
Volumen: 108 Número: 1
Páginas:
WOS Id: 001149264200001
ID de PubMed: 38280035
imagen hybrid, All Open Access; Hybrid Gold Open Access

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