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Safety and Immunogenicity of Betuvax-CoV-2, an RBD-Fc-Based SARS-CoV-2 Recombinant Vaccine: Preliminary Results of the First-in-Human, Randomized, Double-Blind, Placebo-Controlled Phase I/II Clinical Trial

COVID-19, being a life-threatening infection that evolves rapidly, remains a major public health concern calling for the development of vaccines with broad protection against different pathogenic strains and high immunogenicity. Aside from this, other concerns in mass immunization settings are also...

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Autores principales: Kudriavtsev, Aleksandr V., Vakhrusheva, Anna V., Kryuchkov, Nickolay A., Frolova, Maria E., Blagodatskikh, Konstantin A., Ivanishin, Taras V., Djonovic, Milana, Romanovskaya-Romanko, Ekaterina A., Kovalenko, Anton N., Lioznov, Dmitry A., Zubkova, Tatiana G., Teplykh, Svetlana V., Oseshnyuk, Rodion A., Stukova, Marina A., Isaev, Artur A., Krasilnikov, Igor V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9965088/
https://www.ncbi.nlm.nih.gov/pubmed/36851204
http://dx.doi.org/10.3390/vaccines11020326
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author Kudriavtsev, Aleksandr V.
Vakhrusheva, Anna V.
Kryuchkov, Nickolay A.
Frolova, Maria E.
Blagodatskikh, Konstantin A.
Ivanishin, Taras V.
Djonovic, Milana
Romanovskaya-Romanko, Ekaterina A.
Kovalenko, Anton N.
Lioznov, Dmitry A.
Zubkova, Tatiana G.
Teplykh, Svetlana V.
Oseshnyuk, Rodion A.
Stukova, Marina A.
Isaev, Artur A.
Krasilnikov, Igor V.
author_facet Kudriavtsev, Aleksandr V.
Vakhrusheva, Anna V.
Kryuchkov, Nickolay A.
Frolova, Maria E.
Blagodatskikh, Konstantin A.
Ivanishin, Taras V.
Djonovic, Milana
Romanovskaya-Romanko, Ekaterina A.
Kovalenko, Anton N.
Lioznov, Dmitry A.
Zubkova, Tatiana G.
Teplykh, Svetlana V.
Oseshnyuk, Rodion A.
Stukova, Marina A.
Isaev, Artur A.
Krasilnikov, Igor V.
author_sort Kudriavtsev, Aleksandr V.
collection PubMed
description COVID-19, being a life-threatening infection that evolves rapidly, remains a major public health concern calling for the development of vaccines with broad protection against different pathogenic strains and high immunogenicity. Aside from this, other concerns in mass immunization settings are also the scalability of production and relative affordability of the technology. In that regard, adjuvanted protein vaccines with particles mimicking the virus stand out among known vaccine technologies. The “Betuvax-CoV-2” vaccine, developed on the basis of a recombinant protein and an adjuvant, has already been tested in preclinical studies and has advanced to clinical evaluation. Open, double-blinded, placebo-controlled, randomized phase I/II clinical trial of the “Betuvax-CoV-2,” recombinant protein subunit vaccine based on the S-protein RBD fused with the Fc-fragment of IgG, was conducted to evaluate safety and immunogenicity in response to the vaccination. Methods: In the phase I/II clinical trial, 116 healthy adult men and women, ages 18–58, were enrolled: 20 in Stage I, and 96 in Stage II. In Stage I, 20 µg of the vaccine was administered intramuscularly on day 2, and either 5 µg (group 1) or 20 µg (group 2) on day 30. In Stage II, 20 µg of the vaccine was administered intramuscularly on day 2, and either 5 µg (group 3) or 20 µg (group 4) on day 30. In group 5, both injections were replaced with placebo. The primary outcome measures were safety (number of participants with adverse events throughout the study) and antigen-specific humoral immunity (SARS-CoV-2-specific antibodies measured by ELISA and CMIA). Antigen-specific cell-mediated immunity and changes in neutralizing antibodies (detected with a SARS-CoV-2 neutralization assay) were measured as a secondary outcome. The trial is registered with ClinicalTrials.gov (Study Identifier: NCT05270954). Findings: Both vaccine formulations (20 µg + 5 µg and 20 µg + 20 µg) were safe and well tolerated. Most adverse events were mild, and no serious adverse events were detected. On day 51,anti-SARS-CoV-2 total and IgG antibody titers and anti-SARS-CoV-2 neutralizing antibodies were significantly higher in the vaccine groups (both formulations) than in the placebo. A more pronounced CD4+-mediated immune response was observed in the group of volunteers administered with the 20 + 20 μg vaccine formulation. Interpretations: RBD-Fc-based COVID-19 “Betuvax-CoV-2” vaccine in doses (20 + 5 µg and 20 + 20 µg) demonstrated an excellent safety profile and induced a strong humoral response. Further research on the protective effectiveness of the “Betuvax-CoV-2” vaccine for the prevention of COVID-19 is on its way.
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spelling pubmed-99650882023-02-26 Safety and Immunogenicity of Betuvax-CoV-2, an RBD-Fc-Based SARS-CoV-2 Recombinant Vaccine: Preliminary Results of the First-in-Human, Randomized, Double-Blind, Placebo-Controlled Phase I/II Clinical Trial Kudriavtsev, Aleksandr V. Vakhrusheva, Anna V. Kryuchkov, Nickolay A. Frolova, Maria E. Blagodatskikh, Konstantin A. Ivanishin, Taras V. Djonovic, Milana Romanovskaya-Romanko, Ekaterina A. Kovalenko, Anton N. Lioznov, Dmitry A. Zubkova, Tatiana G. Teplykh, Svetlana V. Oseshnyuk, Rodion A. Stukova, Marina A. Isaev, Artur A. Krasilnikov, Igor V. Vaccines (Basel) Article COVID-19, being a life-threatening infection that evolves rapidly, remains a major public health concern calling for the development of vaccines with broad protection against different pathogenic strains and high immunogenicity. Aside from this, other concerns in mass immunization settings are also the scalability of production and relative affordability of the technology. In that regard, adjuvanted protein vaccines with particles mimicking the virus stand out among known vaccine technologies. The “Betuvax-CoV-2” vaccine, developed on the basis of a recombinant protein and an adjuvant, has already been tested in preclinical studies and has advanced to clinical evaluation. Open, double-blinded, placebo-controlled, randomized phase I/II clinical trial of the “Betuvax-CoV-2,” recombinant protein subunit vaccine based on the S-protein RBD fused with the Fc-fragment of IgG, was conducted to evaluate safety and immunogenicity in response to the vaccination. Methods: In the phase I/II clinical trial, 116 healthy adult men and women, ages 18–58, were enrolled: 20 in Stage I, and 96 in Stage II. In Stage I, 20 µg of the vaccine was administered intramuscularly on day 2, and either 5 µg (group 1) or 20 µg (group 2) on day 30. In Stage II, 20 µg of the vaccine was administered intramuscularly on day 2, and either 5 µg (group 3) or 20 µg (group 4) on day 30. In group 5, both injections were replaced with placebo. The primary outcome measures were safety (number of participants with adverse events throughout the study) and antigen-specific humoral immunity (SARS-CoV-2-specific antibodies measured by ELISA and CMIA). Antigen-specific cell-mediated immunity and changes in neutralizing antibodies (detected with a SARS-CoV-2 neutralization assay) were measured as a secondary outcome. The trial is registered with ClinicalTrials.gov (Study Identifier: NCT05270954). Findings: Both vaccine formulations (20 µg + 5 µg and 20 µg + 20 µg) were safe and well tolerated. Most adverse events were mild, and no serious adverse events were detected. On day 51,anti-SARS-CoV-2 total and IgG antibody titers and anti-SARS-CoV-2 neutralizing antibodies were significantly higher in the vaccine groups (both formulations) than in the placebo. A more pronounced CD4+-mediated immune response was observed in the group of volunteers administered with the 20 + 20 μg vaccine formulation. Interpretations: RBD-Fc-based COVID-19 “Betuvax-CoV-2” vaccine in doses (20 + 5 µg and 20 + 20 µg) demonstrated an excellent safety profile and induced a strong humoral response. Further research on the protective effectiveness of the “Betuvax-CoV-2” vaccine for the prevention of COVID-19 is on its way. MDPI 2023-02-01 /pmc/articles/PMC9965088/ /pubmed/36851204 http://dx.doi.org/10.3390/vaccines11020326 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kudriavtsev, Aleksandr V.
Vakhrusheva, Anna V.
Kryuchkov, Nickolay A.
Frolova, Maria E.
Blagodatskikh, Konstantin A.
Ivanishin, Taras V.
Djonovic, Milana
Romanovskaya-Romanko, Ekaterina A.
Kovalenko, Anton N.
Lioznov, Dmitry A.
Zubkova, Tatiana G.
Teplykh, Svetlana V.
Oseshnyuk, Rodion A.
Stukova, Marina A.
Isaev, Artur A.
Krasilnikov, Igor V.
Safety and Immunogenicity of Betuvax-CoV-2, an RBD-Fc-Based SARS-CoV-2 Recombinant Vaccine: Preliminary Results of the First-in-Human, Randomized, Double-Blind, Placebo-Controlled Phase I/II Clinical Trial
title Safety and Immunogenicity of Betuvax-CoV-2, an RBD-Fc-Based SARS-CoV-2 Recombinant Vaccine: Preliminary Results of the First-in-Human, Randomized, Double-Blind, Placebo-Controlled Phase I/II Clinical Trial
title_full Safety and Immunogenicity of Betuvax-CoV-2, an RBD-Fc-Based SARS-CoV-2 Recombinant Vaccine: Preliminary Results of the First-in-Human, Randomized, Double-Blind, Placebo-Controlled Phase I/II Clinical Trial
title_fullStr Safety and Immunogenicity of Betuvax-CoV-2, an RBD-Fc-Based SARS-CoV-2 Recombinant Vaccine: Preliminary Results of the First-in-Human, Randomized, Double-Blind, Placebo-Controlled Phase I/II Clinical Trial
title_full_unstemmed Safety and Immunogenicity of Betuvax-CoV-2, an RBD-Fc-Based SARS-CoV-2 Recombinant Vaccine: Preliminary Results of the First-in-Human, Randomized, Double-Blind, Placebo-Controlled Phase I/II Clinical Trial
title_short Safety and Immunogenicity of Betuvax-CoV-2, an RBD-Fc-Based SARS-CoV-2 Recombinant Vaccine: Preliminary Results of the First-in-Human, Randomized, Double-Blind, Placebo-Controlled Phase I/II Clinical Trial
title_sort safety and immunogenicity of betuvax-cov-2, an rbd-fc-based sars-cov-2 recombinant vaccine: preliminary results of the first-in-human, randomized, double-blind, placebo-controlled phase i/ii clinical trial
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9965088/
https://www.ncbi.nlm.nih.gov/pubmed/36851204
http://dx.doi.org/10.3390/vaccines11020326
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