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.

The COVID-19 pandemic is ongoing, and the need for safe and effective vaccines to prevent infection and to control spread of the virus remains urgent. Here, we report the development of a SARS-CoV-2 subunit vaccine candidate (Betuvax-CoV-2) based on RBD and SD1 domains of the spike (S) protein fused to a human IgG1 Fc fragment. The antigen is adsorbed on betulin adjuvant, forming spherical particles with a size of 100–180 nm, mimicking the size of viral particles. Here we confirm the potent immunostimulatory activity of betulin adjuvant, and demonstrate that two immunizations of mice with Betuvax-CoV-2 elicited high titers of RBD-specific antibodies. The candidate vaccine was also effective in stimulating a neutralizing antibody response and T cell immunity. The results indicate that Betuvax-CoV-2 has good potential for further development as an effective vaccine against SARS-CoV-2.

Public health threat coming from a rapidly developing COVID-19 pandemic calls for developing safe and effective vaccines with innovative designs. This paper presents preclinical trial results of “Betuvax-CoV-2”, a vaccine developed as a subunit vaccine containing a recombinant RBD-Fc fusion protein and betulin-based spherical virus-like nanoparticles as an adjuvant (“Betuspheres”). The study aimed to demonstrate vaccine safety in mice, rats, and Chinchilla rabbits through acute, subchronic, and reproductive toxicity studies. Along with safety, the vaccine demonstrated protective efficacy through SARS-CoV-2-neutralizing antibody production in mice, rats, hamsters, rabbits, and primates (rhesus macaque), and lung damage and infection protection in hamsters and rhesus macaque model. Eventually, “Betuvax-CoV-2” was proved to confer superior efficacy and protection against the SARS-CoV-2 in preclinical studies. Based on the above results, the vaccine was enabled to enter clinical trials that are currently underway.

The development of an effective combined vaccine represents a crucial strategy for preventing outbreaks of infectious diseases and reducing the burden on healthcare resources. Developing a combined vaccine against both influenza and the coronavirus is a promising approach, but it is still in the early stages of development. This paper reports on a novel combined pentavalent candidate vaccine that has shown promising results in mice, with statistically significant differences in mean antibody titer against the coronavirus and the influenza antigens compared to placebo. We have shown that the coronavirus antigen is capable of inducing an immune response autonomously, regardless of the presence of the influenza antigens in a combined vaccine. On the other hand, the presence of the coronavirus antigen in a combined vaccine showed to enhance the immune response against some of the studied influenza antigens, suggesting that these antigens may act in synergy and elicit an enhanced immune response. The absence of dose-dependent difference in mean antibody titer within the same antigenic groups of vaccine preparations suggested that even small amounts of the coronavirus and the influenza antigens could induce an immune response just as good as high-dose vaccine preparations, which certainly has important safety and cost implications. The vaccine is soon to be ready for clinical trials and mass production.

Background. Preventive vaccination is a vitally important strategic aspect of protection of the population against severe effects of influenza epidemics. The priority attention is given to development of effective tetravalent vaccines containing antigens of two influenza A lineages (H1N1, H3N2) and two influenza B lineages (Victoria and Yamagata) in combination with immunoadjuvants.The aim of the work was to conduct the preclinical study of the immunogenicity and protective efficacy of the innovative tetravalent subunit vaccine containing antigens of influenza A and B viruses as well as a corpuscular adjuvant.Materials and methods. The study was conducted using female BALB/c mice. The tetravalent vaccine and monovalent intermediate vaccines combined with a betulin adjuvant were injected intraperitoneally two times at a 14-day interval. The immunogenic activity was measured by the hemagglutination inhibition assay. The protective activity of the vaccine was assessed by changes in the viral load, body weight and survival rates using the mouse model of fatal influenza A H1N1 virus infection.Results. The mice vaccinated with the adjuvanted quadrivalent subunit influenza vaccine produced antibodies against all four influenza viruses included in the vaccine; the mean antibody titers in the hemagglutination inhibition assay were above 1 : 40. The second-dose vaccination induced a significant increase in levels of antibodies against all four influenza viruses. The dose of the quadrivalent subunit adjuvanted vaccine containing 5 µg of each antigen and 200 µg of the adjuvant provided a 100% survival rate in mice and significantly decreased lung viral titers (more than 3 lg TCID50) in the mouse model of influenza pneumonia.Conclusion. The quadrivalent subunit vaccine with the betulin-based corpuscular adjuvant demonstrates high immunogenicity in laboratory mice and provides protection against fatal pneumonia caused by the influenza A virus subtype H1N1.

SARS-CoV-2, the causal agent of the COVID-19 pandemic, is characterized by rapid evolution, which poses a significant public health challenge. Effective vaccines that provide robust protection, elicit strong immune responses, exhibit favorable safety profiles, and enable cost-effective large-scale production are crucial. The RBD-Fc-based Betuvax-CoV-2 vaccine has previously demonstrated a favorable safety profile and induced a significant anti-SARS-CoV-2 humoral immune response in clinical trials. Due to the rapid evolution and emergence of new SARS-CoV-2 strains, the relevance of bivalent vaccine formulations has increased. Methods: This study compared the neutralizing capacity of monovalent and bivalent vaccine formulations against different SARS-CoV-2 strains detected with a SARS-CoV-2 microneutralization assay (MNT). Findings: The monovalent Wuhan-based vaccine generated neutralizing antibodies against the Wuhan and Omicron BA.2 variants but not the distinct Omicron BQ.1 strain. Conversely, the monovalent BA.2-based vaccine induced neutralizing antibodies against both Omicron strains but not Wuhan. While the bivalent Wuhan and BA.2-based vaccine was effective against strains containing the same antigens, it was insufficient to neutralize the distinctive BQ.1 strain at a small dosage. Interpretation: These findings suggest that the vaccine composition should closely match the circulating SARS-CoV-2 strain to elicit the optimal neutralizing antibody response and include the appropriate dosage. Moreover, this study did not find additional advantages of using the bivalent form over the monovalent form for the vaccination against a single prevailing SARS-CoV-2 strain.