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.

Autor:	Kudriavtsev AV; Betuvax LLC, 121096 Moscow, Russia., Vakhrusheva AV; Betuvax LLC, 121096 Moscow, Russia., Kryuchkov NA; Clinical Excellence Group LLC, 127051 Moscow, Russia., Frolova ME; PJSC Human Stem Cells Institute, 129110 Moscow, Russia., Blagodatskikh KA; Center of Genetics and Reproductive Medicine 'Genetico', 119333 Moscow, Russia., Ivanishin TV; Betuvax LLC, 121096 Moscow, Russia.; PJSC Human Stem Cells Institute, 129110 Moscow, Russia., Djonovic M; PJSC Human Stem Cells Institute, 129110 Moscow, Russia., Romanovskaya-Romanko EA; Department of Vaccinology, Smorodintsev Research Institute of Influenza, Ministry of Health of the Russian Federation, 197376 Saint Petersburg, Russia., Kovalenko AN; Clinical Excellence Group LLC, 127051 Moscow, Russia., Lioznov DA; Department of Vaccinology, Smorodintsev Research Institute of Influenza, Ministry of Health of the Russian Federation, 197376 Saint Petersburg, Russia., Zubkova TG; Department of Vaccinology, Smorodintsev Research Institute of Influenza, Ministry of Health of the Russian Federation, 197376 Saint Petersburg, Russia., Teplykh SV; Professor Clinic LLC, 614070 Perm, Russia., Oseshnyuk RA; Ecosafety Center LLC, 195000 Saint Petersburg, Russia., Stukova MA; Department of Vaccinology, Smorodintsev Research Institute of Influenza, Ministry of Health of the Russian Federation, 197376 Saint Petersburg, Russia., Isaev AA; PJSC Human Stem Cells Institute, 129110 Moscow, Russia., Krasilnikov IV; Department of Vaccinology, Smorodintsev Research Institute of Influenza, Ministry of Health of the Russian Federation, 197376 Saint Petersburg, Russia.; Biotechnology Developments LLC, 119285 Moscow, Russia.
Jazyk:	angličtina
Zdroj:	Vaccines [Vaccines (Basel)] 2023 Feb 01; Vol. 11 (2). Date of Electronic Publication: 2023 Feb 01.
DOI:	10.3390/vaccines11020326
Abstrakt:	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.
Databáze:	MEDLINE
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