Oral administration of a recombinant modified RBD antigen of SARS-CoV-2 as a possible immunostimulant for the care of COVID-19
Abstract Background Developing effective vaccines against SARS-CoV-2 that consider manufacturing limitations, equitable access, and acceptance is necessary for developing platforms to produce antigens that can be efficiently presented for generating neutralizing antibodies and as a model for new vac...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2024-02-01
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| Series: | Microbial Cell Factories |
| Online Access: | https://doi.org/10.1186/s12934-024-02320-5 |
| _version_ | 1797272250438647808 |
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| author | Norma A. Valdez‑Cruz Diego Rosiles-Becerril Constanza E. Martínez-Olivares Enrique García‑Hernández Laura Cobos-Marín Daniel Garzón Francisco E. López-Salas Guadalupe Zavala Axel Luviano Alejandro Olvera Alejandro Alagón Octavio T. Ramírez Mauricio A. Trujillo‑Roldán |
| author_facet | Norma A. Valdez‑Cruz Diego Rosiles-Becerril Constanza E. Martínez-Olivares Enrique García‑Hernández Laura Cobos-Marín Daniel Garzón Francisco E. López-Salas Guadalupe Zavala Axel Luviano Alejandro Olvera Alejandro Alagón Octavio T. Ramírez Mauricio A. Trujillo‑Roldán |
| author_sort | Norma A. Valdez‑Cruz |
| collection | DOAJ |
| description | Abstract Background Developing effective vaccines against SARS-CoV-2 that consider manufacturing limitations, equitable access, and acceptance is necessary for developing platforms to produce antigens that can be efficiently presented for generating neutralizing antibodies and as a model for new vaccines. Results This work presents the development of an applicable technology through the oral administration of the SARS-CoV-2 RBD antigen fused with a peptide to improve its antigenic presentation. We focused on the development and production of the recombinant receptor binding domain (RBD) produced in E. coli modified with the addition of amino acids extension designed to improve antigen presentation. The production was carried out in shake flask and bioreactor cultures, obtaining around 200 mg/L of the antigen. The peptide-fused RBD and peptide-free RBD proteins were characterized and compared using SDS-PAGE gel, high-performance chromatography, and circular dichroism. The peptide-fused RBD was formulated in an oil-in-water emulsion for oral mice immunization. The peptide-fused RBD, compared to RBD, induced robust IgG production in mice, capable of recognizing the recombinant RBD in Enzyme-linked immunosorbent assays. In addition, the peptide-fused RBD generated neutralizing antibodies in the sera of the dosed mice. The formulation showed no reactive episodes and no changes in temperature or vomiting. Conclusions Our study demonstrated the effectiveness of the designed peptide added to the RBD to improve antigen immunostimulation by oral administration. Graphical Abstract |
| first_indexed | 2024-03-07T14:25:41Z |
| format | Article |
| id | doaj.art-e13a32445db2407eaf766e0d1f636291 |
| institution | Directory Open Access Journal |
| issn | 1475-2859 |
| language | English |
| last_indexed | 2024-03-07T14:25:41Z |
| publishDate | 2024-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Microbial Cell Factories |
| spelling | doaj.art-e13a32445db2407eaf766e0d1f6362912024-03-06T08:06:27ZengBMCMicrobial Cell Factories1475-28592024-02-0123112210.1186/s12934-024-02320-5Oral administration of a recombinant modified RBD antigen of SARS-CoV-2 as a possible immunostimulant for the care of COVID-19Norma A. Valdez‑Cruz0Diego Rosiles-Becerril1Constanza E. Martínez-Olivares2Enrique García‑Hernández3Laura Cobos-Marín4Daniel Garzón5Francisco E. López-Salas6Guadalupe Zavala7Axel Luviano8Alejandro Olvera9Alejandro Alagón10Octavio T. Ramírez11Mauricio A. Trujillo‑Roldán12Departamento de Biología Molecular y Biotecnología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de MéxicoDepartamento de Biología Molecular y Biotecnología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de MéxicoDepartamento de Biología Molecular y Biotecnología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de MéxicoInstituto de Química, Universidad Nacional Autónoma de MéxicoDepartamento de Microbiología e Inmunología, Facultad de Medicina Veterinaria y Zootecnia, Universidad Nacional Autónoma de MéxicoUnidad de Modelos Biológicos, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de MéxicoDepartamento de Biología Molecular y Biotecnología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de MéxicoUnidad de Microscopia Electrónica, Instituto de Biotecnología, Universidad Nacional Autónoma de MéxicoDepartamento de Genética del Desarrollo y Fisiologia Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de MéxicoDepartamento de Biología Molecular y Bioprocesos, Instituto de Biotecnología, Universidad Nacional Autónoma de MéxicoDepartamento de Biología Molecular y Bioprocesos, Instituto de Biotecnología, Universidad Nacional Autónoma de MéxicoDepartamento de Biología Molecular y Bioprocesos, Instituto de Biotecnología, Universidad Nacional Autónoma de MéxicoDepartamento de Biología Molecular y Biotecnología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de MéxicoAbstract Background Developing effective vaccines against SARS-CoV-2 that consider manufacturing limitations, equitable access, and acceptance is necessary for developing platforms to produce antigens that can be efficiently presented for generating neutralizing antibodies and as a model for new vaccines. Results This work presents the development of an applicable technology through the oral administration of the SARS-CoV-2 RBD antigen fused with a peptide to improve its antigenic presentation. We focused on the development and production of the recombinant receptor binding domain (RBD) produced in E. coli modified with the addition of amino acids extension designed to improve antigen presentation. The production was carried out in shake flask and bioreactor cultures, obtaining around 200 mg/L of the antigen. The peptide-fused RBD and peptide-free RBD proteins were characterized and compared using SDS-PAGE gel, high-performance chromatography, and circular dichroism. The peptide-fused RBD was formulated in an oil-in-water emulsion for oral mice immunization. The peptide-fused RBD, compared to RBD, induced robust IgG production in mice, capable of recognizing the recombinant RBD in Enzyme-linked immunosorbent assays. In addition, the peptide-fused RBD generated neutralizing antibodies in the sera of the dosed mice. The formulation showed no reactive episodes and no changes in temperature or vomiting. Conclusions Our study demonstrated the effectiveness of the designed peptide added to the RBD to improve antigen immunostimulation by oral administration. Graphical Abstracthttps://doi.org/10.1186/s12934-024-02320-5 |
| spellingShingle | Norma A. Valdez‑Cruz Diego Rosiles-Becerril Constanza E. Martínez-Olivares Enrique García‑Hernández Laura Cobos-Marín Daniel Garzón Francisco E. López-Salas Guadalupe Zavala Axel Luviano Alejandro Olvera Alejandro Alagón Octavio T. Ramírez Mauricio A. Trujillo‑Roldán Oral administration of a recombinant modified RBD antigen of SARS-CoV-2 as a possible immunostimulant for the care of COVID-19 Microbial Cell Factories |
| title | Oral administration of a recombinant modified RBD antigen of SARS-CoV-2 as a possible immunostimulant for the care of COVID-19 |
| title_full | Oral administration of a recombinant modified RBD antigen of SARS-CoV-2 as a possible immunostimulant for the care of COVID-19 |
| title_fullStr | Oral administration of a recombinant modified RBD antigen of SARS-CoV-2 as a possible immunostimulant for the care of COVID-19 |
| title_full_unstemmed | Oral administration of a recombinant modified RBD antigen of SARS-CoV-2 as a possible immunostimulant for the care of COVID-19 |
| title_short | Oral administration of a recombinant modified RBD antigen of SARS-CoV-2 as a possible immunostimulant for the care of COVID-19 |
| title_sort | oral administration of a recombinant modified rbd antigen of sars cov 2 as a possible immunostimulant for the care of covid 19 |
| url | https://doi.org/10.1186/s12934-024-02320-5 |
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