A Novel Bacterial Protease Inhibitor Adjuvant in RBD-Based COVID-19 Vaccine Formulations Containing Alum Increases Neutralizing Antibodies, Specific Germinal Center B Cells and Confers Protection Against SARS-CoV-2 Infection in Mice
In this work, we evaluated recombinant receptor binding domain (RBD)-based vaccine formulation prototypes with potential for further clinical development. We assessed different formulations containing RBD plus alum, AddaS03, AddaVax, or the combination of alum and U-Omp19: a novel Brucella spp. prot...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-02-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.844837/full |
| _version_ | 1818199766673129472 |
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| author | Lorena M. Coria Lucas M. Saposnik Celeste Pueblas Castro Eliana F. Castro Eliana F. Castro Laura A. Bruno William B. Stone Paula S. Pérez Maria Laura Darriba Lucia B. Chemes Julieta Alcain Ignacio Mazzitelli Augusto Varese Melina Salvatori Albert J. Auguste Albert J. Auguste Diego E. Álvarez Karina A. Pasquevich Juliana Cassataro |
| author_facet | Lorena M. Coria Lucas M. Saposnik Celeste Pueblas Castro Eliana F. Castro Eliana F. Castro Laura A. Bruno William B. Stone Paula S. Pérez Maria Laura Darriba Lucia B. Chemes Julieta Alcain Ignacio Mazzitelli Augusto Varese Melina Salvatori Albert J. Auguste Albert J. Auguste Diego E. Álvarez Karina A. Pasquevich Juliana Cassataro |
| author_sort | Lorena M. Coria |
| collection | DOAJ |
| description | In this work, we evaluated recombinant receptor binding domain (RBD)-based vaccine formulation prototypes with potential for further clinical development. We assessed different formulations containing RBD plus alum, AddaS03, AddaVax, or the combination of alum and U-Omp19: a novel Brucella spp. protease inhibitor vaccine adjuvant. Results show that the vaccine formulation composed of U-Omp19 and alum as adjuvants has a better performance: it significantly increased mucosal and systemic neutralizing antibodies in comparison to antigen plus alum, AddaVax, or AddaS03. Antibodies induced with the formulation containing U-Omp19 and alum not only increased their neutralization capacity against the ancestral virus but also cross-neutralized alpha, lambda, and gamma variants with similar potency. Furthermore, the addition of U-Omp19 to alum vaccine formulation increased the frequency of RBD-specific geminal center B cells and plasmablasts. Additionally, U-Omp19+alum formulation induced RBD-specific Th1 and CD8+ T-cell responses in spleens and lungs. Finally, this vaccine formulation conferred protection against an intranasal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) challenge of K18-hACE2 mice. |
| first_indexed | 2024-12-12T02:26:59Z |
| format | Article |
| id | doaj.art-7f7101efd88c4e0e81c0f30450a9b387 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-12T02:26:59Z |
| publishDate | 2022-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-7f7101efd88c4e0e81c0f30450a9b3872022-12-22T00:41:31ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-02-011310.3389/fimmu.2022.844837844837A Novel Bacterial Protease Inhibitor Adjuvant in RBD-Based COVID-19 Vaccine Formulations Containing Alum Increases Neutralizing Antibodies, Specific Germinal Center B Cells and Confers Protection Against SARS-CoV-2 Infection in MiceLorena M. Coria0Lucas M. Saposnik1Celeste Pueblas Castro2Eliana F. Castro3Eliana F. Castro4Laura A. Bruno5William B. Stone6Paula S. Pérez7Maria Laura Darriba8Lucia B. Chemes9Julieta Alcain10Ignacio Mazzitelli11Augusto Varese12Melina Salvatori13Albert J. Auguste14Albert J. Auguste15Diego E. Álvarez16Karina A. Pasquevich17Juliana Cassataro18Instituto de Investigaciones Biotecnológicas Dr. Rodolfo A. Ugalde, Universidad Nacional de San Martín, Consejo Nacional de Investigaciones Científicas y Técnicas (UNSAM-CONICET), San Martín, ArgentinaInstituto de Investigaciones Biotecnológicas Dr. Rodolfo A. Ugalde, Universidad Nacional de San Martín, Consejo Nacional de Investigaciones Científicas y Técnicas (UNSAM-CONICET), San Martín, ArgentinaInstituto de Investigaciones Biotecnológicas Dr. Rodolfo A. Ugalde, Universidad Nacional de San Martín, Consejo Nacional de Investigaciones Científicas y Técnicas (UNSAM-CONICET), San Martín, ArgentinaInstituto de Investigaciones Biotecnológicas Dr. Rodolfo A. Ugalde, Universidad Nacional de San Martín, Consejo Nacional de Investigaciones Científicas y Técnicas (UNSAM-CONICET), San Martín, ArgentinaInstituto de Virología e Innovaciones Tecnológicas (IVIT), Centro de Investigaciones en Ciencias Veterinarias y Agronómicas (CICVyA), Instituto Nacional de Tecnología Agropecuaria (INTA)-Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, ArgentinaInstituto de Investigaciones Biotecnológicas Dr. Rodolfo A. Ugalde, Universidad Nacional de San Martín, Consejo Nacional de Investigaciones Científicas y Técnicas (UNSAM-CONICET), San Martín, ArgentinaDepartment of Entomology, College of Agriculture and Life Sciences, Fralin Life Science Institute, Virginia Polytechnic Institute and State University, Blacksburg, VA, United StatesInstituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS, Universidad de Buenos Aires-CONICET), Buenos Aires, ArgentinaInstituto de Investigaciones Biotecnológicas Dr. Rodolfo A. Ugalde, Universidad Nacional de San Martín, Consejo Nacional de Investigaciones Científicas y Técnicas (UNSAM-CONICET), San Martín, ArgentinaInstituto de Investigaciones Biotecnológicas Dr. Rodolfo A. Ugalde, Universidad Nacional de San Martín, Consejo Nacional de Investigaciones Científicas y Técnicas (UNSAM-CONICET), San Martín, ArgentinaInstituto de Investigaciones Biotecnológicas Dr. Rodolfo A. Ugalde, Universidad Nacional de San Martín, Consejo Nacional de Investigaciones Científicas y Técnicas (UNSAM-CONICET), San Martín, ArgentinaInstituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS, Universidad de Buenos Aires-CONICET), Buenos Aires, ArgentinaInstituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS, Universidad de Buenos Aires-CONICET), Buenos Aires, ArgentinaInstituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS, Universidad de Buenos Aires-CONICET), Buenos Aires, ArgentinaDepartment of Entomology, College of Agriculture and Life Sciences, Fralin Life Science Institute, Virginia Polytechnic Institute and State University, Blacksburg, VA, United StatesCenter for Emerging, Zoonotic, and Arthropod-borne Pathogens, Virginia Polytechnic Institute and State University, Blacksburg, VA, United StatesInstituto de Investigaciones Biotecnológicas Dr. Rodolfo A. Ugalde, Universidad Nacional de San Martín, Consejo Nacional de Investigaciones Científicas y Técnicas (UNSAM-CONICET), San Martín, ArgentinaInstituto de Investigaciones Biotecnológicas Dr. Rodolfo A. Ugalde, Universidad Nacional de San Martín, Consejo Nacional de Investigaciones Científicas y Técnicas (UNSAM-CONICET), San Martín, ArgentinaInstituto de Investigaciones Biotecnológicas Dr. Rodolfo A. Ugalde, Universidad Nacional de San Martín, Consejo Nacional de Investigaciones Científicas y Técnicas (UNSAM-CONICET), San Martín, ArgentinaIn this work, we evaluated recombinant receptor binding domain (RBD)-based vaccine formulation prototypes with potential for further clinical development. We assessed different formulations containing RBD plus alum, AddaS03, AddaVax, or the combination of alum and U-Omp19: a novel Brucella spp. protease inhibitor vaccine adjuvant. Results show that the vaccine formulation composed of U-Omp19 and alum as adjuvants has a better performance: it significantly increased mucosal and systemic neutralizing antibodies in comparison to antigen plus alum, AddaVax, or AddaS03. Antibodies induced with the formulation containing U-Omp19 and alum not only increased their neutralization capacity against the ancestral virus but also cross-neutralized alpha, lambda, and gamma variants with similar potency. Furthermore, the addition of U-Omp19 to alum vaccine formulation increased the frequency of RBD-specific geminal center B cells and plasmablasts. Additionally, U-Omp19+alum formulation induced RBD-specific Th1 and CD8+ T-cell responses in spleens and lungs. Finally, this vaccine formulation conferred protection against an intranasal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) challenge of K18-hACE2 mice.https://www.frontiersin.org/articles/10.3389/fimmu.2022.844837/fulladjuvantprotease inhibitorSARS- CoV-2U-Omp19germinal center cells |
| spellingShingle | Lorena M. Coria Lucas M. Saposnik Celeste Pueblas Castro Eliana F. Castro Eliana F. Castro Laura A. Bruno William B. Stone Paula S. Pérez Maria Laura Darriba Lucia B. Chemes Julieta Alcain Ignacio Mazzitelli Augusto Varese Melina Salvatori Albert J. Auguste Albert J. Auguste Diego E. Álvarez Karina A. Pasquevich Juliana Cassataro A Novel Bacterial Protease Inhibitor Adjuvant in RBD-Based COVID-19 Vaccine Formulations Containing Alum Increases Neutralizing Antibodies, Specific Germinal Center B Cells and Confers Protection Against SARS-CoV-2 Infection in Mice Frontiers in Immunology adjuvant protease inhibitor SARS- CoV-2 U-Omp19 germinal center cells |
| title | A Novel Bacterial Protease Inhibitor Adjuvant in RBD-Based COVID-19 Vaccine Formulations Containing Alum Increases Neutralizing Antibodies, Specific Germinal Center B Cells and Confers Protection Against SARS-CoV-2 Infection in Mice |
| title_full | A Novel Bacterial Protease Inhibitor Adjuvant in RBD-Based COVID-19 Vaccine Formulations Containing Alum Increases Neutralizing Antibodies, Specific Germinal Center B Cells and Confers Protection Against SARS-CoV-2 Infection in Mice |
| title_fullStr | A Novel Bacterial Protease Inhibitor Adjuvant in RBD-Based COVID-19 Vaccine Formulations Containing Alum Increases Neutralizing Antibodies, Specific Germinal Center B Cells and Confers Protection Against SARS-CoV-2 Infection in Mice |
| title_full_unstemmed | A Novel Bacterial Protease Inhibitor Adjuvant in RBD-Based COVID-19 Vaccine Formulations Containing Alum Increases Neutralizing Antibodies, Specific Germinal Center B Cells and Confers Protection Against SARS-CoV-2 Infection in Mice |
| title_short | A Novel Bacterial Protease Inhibitor Adjuvant in RBD-Based COVID-19 Vaccine Formulations Containing Alum Increases Neutralizing Antibodies, Specific Germinal Center B Cells and Confers Protection Against SARS-CoV-2 Infection in Mice |
| title_sort | novel bacterial protease inhibitor adjuvant in rbd based covid 19 vaccine formulations containing alum increases neutralizing antibodies specific germinal center b cells and confers protection against sars cov 2 infection in mice |
| topic | adjuvant protease inhibitor SARS- CoV-2 U-Omp19 germinal center cells |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.844837/full |
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