SARS-CoV-2 Subunit Virus-like Vaccine Demonstrates High Safety Profile and Protective Efficacy: Preclinical Study

Vakhrusheva, Anna; Kudriavtsev, Aleksandr V.; Kryuchkov, Nickolay A.; Деев, Р. В.; Frolova, Maria E.; Blagodatskikh, Konstantin A.; Djonovic, Milana; Nedorubov, Andrey; Odintsova, Elena S.; Иванов, Александр Викторович; Romanovskaya-Romanko, Ekaterina A.; Stukova, Marina; Исаев, А. А.; Красильников, И. В.

doi:10.3390/vaccines10081290

Cited by 3 publications

(5 citation statements)

References 31 publications

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“…The “Betuvax-CoV-2” vaccine was developed as a subunit vaccine containing a recombinant RBD-Fc fusion protein absorbed on the surface of the betulin-based spherical nanoparticles (“Betuspheres”) mimicking the virus and enhancing the immune response [ 3 ]. Preclinical studies [ 4 ] showed a high safety profile of the “Betuvax-CoV-2” vaccine in various animal models, high titers of neutralizing antibodies, and protectivity against the virus infection and lung damage. In this study, we aim to assess the safety and immunogenicity of the novel subunit COVID-19 vaccine “Betuvax-CoV-2” in Russian adults ages 18−58.…”

Section: Introductionmentioning

confidence: 99%

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

Kudriavtsev¹,

Vakhrusheva²,

Kryuchkov

et al. 2023

Vaccines

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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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Section: Introductionmentioning

confidence: 99%

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

Kudriavtsev¹,

Vakhrusheva²,

Kryuchkov

et al. 2023

Vaccines

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“…Although this study demonstrated scalability up to a 2 L bioreactor, transitioning from laboratory-scale bioreactors to larger industrial-scale vessels to produce material for preclinical toxicology study can be readily achievable with a scale-up approach with parameters such as power/volume, mass transfer coefficient, and tip speed [ 2 , 62 ]. Given our current production performance, a 50 L scale production would be sufficient for comprehensive toxicological evaluations and protective immunization studies [ 63 , 64 ].…”

Section: Discussionmentioning

confidence: 99%

Rapid and Scalable Production of Functional SARS-CoV-2 Virus-like Particles (VLPs) by a Stable HEK293 Cell Pool

Puarattana-aroonkorn,

Tharakaraman,

Suriyawipada

et al. 2024

Vaccines

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At times of pandemics, such as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the situation demands rapid development and production timelines of safe and effective vaccines for delivering life-saving medications quickly to patients. Typical biologics production relies on using the lengthy and arduous approach of stable single-cell clones. Here, we used an alternative approach, a stable cell pool that takes only weeks to generate compared to a stable single-cell clone that needs several months to complete. We employed the membrane, envelope, and highly immunogenic spike proteins of SARS-CoV-2 to produce virus-like particles (VLPs) using the HEK293-F cell line as a host system with an economical transfection reagent. The cell pool showed the stability of protein expression for more than one month. We demonstrated that the production of SARS-CoV-2 VLPs using this cell pool was scalable up to a stirred-tank 2 L bioreactor in fed-batch mode. The purified VLPs were properly assembled, and their size was consistent with the authentic virus. Our particles were functional as they specifically entered the cell that naturally expresses ACE-2. Notably, this work reports a practical and cost-effective manufacturing platform for scalable SARS-CoV-2 VLPs production and chromatographic purification.

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“…38 In the clinic, Matrix-M nanoparticles make up 20.3% of unique vaccine formulations and $25% of total trials among the nanoparticle category (Figure 3a) and are cur- trigger the immune system similarly. 65,66 In recent studies on Betuvax-coV02, it demonstrated to be safe and tolerated with mild reactions to the vaccination. There were shown to be specific IgG antibody titers and a strong CD4+ and CD8+ T-cell responses to the antigen.…”

Section: Matrix-mmentioning

confidence: 99%

“…Currently in the clinical landscape, betulin‐based nanoparticles appear in one trial for a COVID‐19 vaccine called Betuvax‐CoV‐2 (NCT05270954). Betuvax‐CoV‐2 contains recombinant RBD‐SD1‐Fc fusion proteins on the surface of a betulin‐based spherical nanoparticles, which is formulated to mimic the SARS‐CoV‐2 virus to trigger the immune system similarly 65,66 . In recent studies on Betuvax‐coV02, it demonstrated to be safe and tolerated with mild reactions to the vaccination.…”

Section: Current Clinical Trialsmentioning

confidence: 99%

“…Betuvax‐CoV‐2 contains recombinant RBD‐SD1‐Fc fusion proteins on the surface of a betulin‐based spherical nanoparticles, which is formulated to mimic the SARS‐CoV‐2 virus to trigger the immune system similarly. 65 , 66 In recent studies on Betuvax‐coV02, it demonstrated to be safe and tolerated with mild reactions to the vaccination. There were shown to be specific IgG antibody titers and a strong CD4+ and CD8+ T‐cell responses to the antigen.…”

Section: Current Clinical Trialsmentioning

confidence: 99%

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Vaccine adjuvants for infectious disease in the clinic

Goetz,

Thotathil,

Zhao

et al. 2024

Bioengineering & Transla Med

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Adjuvants, materials added to vaccines to enhance the resulting immune response, are important components of vaccination that are many times overlooked. While vaccines always include an antigen to tell the body what to vaccinate to, of equal importance the adjuvant provides the how, a significant factor in producing a complete response. The adjuvant space has been slow to develop with the first use of an adjuvant in a licensed vaccine occurring in the 1930s, and remaining the only adjuvant in licensed vaccines for the next 80 years. However, with vaccination at the forefront of protection against new and complex pathogens, it is important to consider all components when designing an effective vaccine. Here we summarize the adjuvant space in licensed vaccines as well as the novel adjuvant space in clinical trials with a specific focus on the materials utilized and their resulting impact on the immune response. We discuss five major categories of adjuvant materials: aluminum salts, nanoparticles, viral vectors, TLR agonists, and emulsions. For each category, we delve into the current clinical trials space, the impact of these materials on vaccination, as well as some of the ways in which they could be improved. Adjuvants present an exciting opportunity to improve vaccine responses and stability, this review will help inform about the current progress of this space.Translational impact statementIn the aftermath of the COVID‐19 pandemic, vaccines for infectious diseases have come into the spotlight. While antigens have always been an important focus of vaccine design, the adjuvant is a significant tool for enhancing the immune response to the vaccine that has been largely underdeveloped. This article provides a broad review of the history of adjuvants and, the current vaccine adjuvant space, and the progress seen in adjuvants in clinical trials. There is specific emphasis on the material landscape for adjuvants and their resulting mechanism of action. Looking ahead, while the novel vaccine adjuvant space features exciting new technologies and materials, there is still a need for more to meet the protective needs of new and complex pathogens.

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SARS-CoV-2 Subunit Virus-like Vaccine Demonstrates High Safety Profile and Protective Efficacy: Preclinical Study

Cited by 3 publications

References 31 publications

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

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

Rapid and Scalable Production of Functional SARS-CoV-2 Virus-like Particles (VLPs) by a Stable HEK293 Cell Pool

Vaccine adjuvants for infectious disease in the clinic

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