Publications by authors named "Karpenko L"

Article Synopsis
  • - The vaccinia virus has been historically used as a smallpox vaccine, but due to its reactogenicity, WHO recommended discontinuation after smallpox was eradicated, leading to a rise in orthopoxvirus infections, notably the 2022 monkeypox epidemic.
  • - Researchers developed modified VACV strains, LAD and LADA, with specific genetic alterations to reduce reactogenicity while enhancing the immune response compared to the original L strain.
  • - Both LAD and LADA strains demonstrated superior cellular immune responses and higher levels of VACV-specific IgG in vaccinated mice, indicating their potential as safer and more effective vaccines against orthopoxvirus infections.
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The mouse paramyxovirus Sendai, which is capable of limited replication in human bronchial epithelial cells without causing disease, is well suited for the development of vector-based intranasal vaccines against respiratory infections, including SARS-CoV-2. Using the Moscow strain of the Sendai virus, we developed a vaccine construct, Sen-Sdelta(M), which expresses the full-length spike (S) protein of the SARS-CoV-2 delta variant. A single intranasal delivery of Sen-Sdelta(M) to Syrian hamsters and BALB/c mice induced high titers of virus-neutralizing antibodies specific to the SARS-CoV-2 delta variant.

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The removal of double-stranded RNA (dsRNA) contaminants during in vitro mRNA synthesis is one of the technological problems to be solved. Apparently, these contaminants are the result of the T7 RNA polymerase side activity. In this study, we used a modified method of mRNA purification based on the selective binding of dsRNA to cellulose in ethanol-containing buffer.

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We studied a needle-free jet injection delivery of an experimental mRNA vaccine encoding the receptor-binding domain of the SARS-CoV-2 S protein (mRNA-RBD). Immunization of BALB/c mice with mRNA-RBD by a needle-free jet injector induced high levels of antibodies with virus-neutralizing activity and a virus-specific T-cell response. The immune response was low in the group of mice that received intramuscular injection of mRNA-RBD.

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Article Synopsis
  • The H5N8 avian influenza virus poses a risk to bird populations and potential human health concerns, necessitating the development of a safe and effective vaccine.
  • Researchers created an experimental pVAX-H5 DNA vaccine that encodes a modified version of the virus's hemagglutinin and tested it on mice, resulting in a strong antibody and T-cell response.
  • Both liquid and lyophilized versions of the pVAX-H5 vaccine provided complete protection for mice against lethal influenza A virus challenges, showing promise as a candidate for combating H5N8.
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In this study, we characterized recombinant hemagglutinin (HA) of influenza A (H5N8) virus produced in Chinese hamster ovary cells (CHO-K1s). Immunochemical analysis showed that the recombinant hemagglutinin was recognized by the serum of ferrets infected with influenza A (H5N8) virus, indicating that its antigenic properties were retained. Two groups of Balb/c mice were immunized with intramuscular injection of recombinant hemagglutinin or propiolactone inactivated A/Astrakhan/3212/2020 (H5N8) influenza virus.

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  • Stabilized trimers of the HIV-1 envelope glycoprotein Env show promise in generating strong and lasting broadly neutralizing antibody responses, making them potential candidates for anti-HIV vaccines.
  • A stable producer of the trimer Env recombinant form CRF63_02A6 was created using CHO-K1 cells, which are commonly used in biotechnology.
  • Immunochemical assays confirmed that these synthesized trimers were recognized by both monoclonal antibodies and sera from HIV-positive patients, indicating their effectiveness for future vaccine development and structural studies.
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A promising approach to the development of new means for preventing infection caused by tick-borne encephalitis virus can be DNA vaccines encoding polyepitope T-cell immunogens. A DNA vaccine pVAX-AG4-ub encoding an artificial polyepitope immunogen that includes cytotoxic and T-helper epitopes from the NS1, NS3, NS5, and E proteins of the tick-borne encephalitis virus has been obtained. The developed construct ensured the synthesis of the corresponding mRNAs in transfected eukaryotic cells.

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Introduction: Nucleic acids represent a promising platform for creating vaccines. One disadvantage of this approach is its relatively low immunogenicity. Electroporation (EP) is an effective way to increase the DNA vaccines immunogenicity.

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An artificial T-cell immunogen consisting of conserved fragments of different proteins of the SARS-CoV-2 virus and its immunogenic properties were studied in BALB/c mice. To create a T-cell immunogen, we used an approach based on the design of artificial antigens that combine many epitopes from the main proteins of the SARS-CoV-2 virus in the one molecule. The gene of the engineered immunogen protein was cloned as part of the pVAX1 plasmid in two versions: with an N-terminal ubiquitin and without it.

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Article Synopsis
  • The study investigates a 94-kDa protein from vaccinia virus (VACV), a truncated version of the cowpox virus's A-type inclusion protein, which is important for the virus's immunogenicity but does not contribute to neutralization.
  • Researchers created a recombinant VACV strain (LIVPΔati) by deleting a gene related to this protein and tested its effects on pathogenicity and immunogenicity in mice.
  • Results showed that LIVPΔati caused less mortality in infected mice and induced a stronger antibody response compared to the parent virus, while both strains elicited similar cell-mediated immunity.
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Vaccination is the most efficient way to prevent infectious diseases. mRNA-based vaccines is a new approach to vaccine development, which have several very useful advantages over other types of vaccines. Since mRNA encodes only the target antigen there is no potential risk of infection as in the case with attenuated or inactivated pathogens.

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Despite the rapid development and approval of several COVID vaccines based on the full-length spike protein, there is a need for safe, potent, and high-volume vaccines. Considering the predominance of the production of neutralizing antibodies targeting the receptor-binding domain (RBD) of S-protein after natural infection or vaccination, it makes sense to choose RBD as a vaccine immunogen. However, due to its small size, RBD exhibits relatively poor immunogenicity.

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DNA and RNA vaccines (nucleic acid-based vaccines) are a promising platform for vaccine development. The first mRNA vaccines (Moderna and Pfizer/BioNTech) were approved in 2020, and a DNA vaccine (Zydus Cadila, India), in 2021. They display unique benefits in the current COVID-19 pandemic.

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Article Synopsis
  • The monkeypox virus outbreak outside Africa in 2022 has highlighted the urgent need for immunization, which could be achieved using a first-generation smallpox vaccine licensed in Russia.
  • Current guidelines recommend transepidermal inoculation (skin scarification), but this method has reliability issues, prompting the exploration of intradermal (i.d.) injection as an alternative vaccination technique.
  • A study compared these two methods in mice, finding no significant difference in antibody responses, but a stronger T-cell immune response with i.d. injection; both methods provided protection against cowpox, while i.d. immunization resulted in a 50% survival rate against a lethal strain of ectromelia virus.
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  • The COVID-19 pandemic highlighted the importance of developing new prophylactic vaccines, including those that combine DNA and protein elements.
  • A combined vaccine was created using the full-length spike protein and the recombinant receptor-binding domain from the SARS-CoV-2 virus, produced in CHO-K1 cells.
  • This combined DNA/protein vaccine demonstrates the advantages of both subunit and DNA vaccines, stimulating both humoral and cellular immune responses.
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Fires are a naturally cyclical factor regulating ecosystems’ function and forming new postfire ecosystems. Peat soils are unique archives that store information about ecological and climatic changes and the history of past fires during the Holocene. The paper presents a reconstruction of the dynamics of fires in the subzone of the middle taiga of Western Siberia in the Holocene.

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Vaccination against SARS-CoV-2 and other viral infections requires safe, effective, and inexpensive vaccines that can be rapidly developed. DNA vaccines are candidates that meet these criteria, but one of their drawbacks is their relatively weak immunogenicity. Electroporation (EP) is an effective way to enhance the immunogenicity of DNA vaccines, but because of the different configurations of the devices that are used for EP, it is necessary to carefully select the conditions of the procedure, including characteristics such as voltage, current strength, number of pulses, etc.

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  • The conventional live smallpox vaccine, based on the vaccinia virus (VACV), has limitations due to high reactogenicity, prompting the need for safer VACV variants with better immune responses.
  • This study explores low-dose VACV variants with genetic modifications that boost immune responses, specifically looking at humoral and T cell-mediated immunity in mice.
  • The research found that the LIVP-A34R*-dA35R variant produced the strongest T cell-mediated immunity and higher antibody levels compared to the parental LIVP strain, suggesting that combining gene modification and deletion enhances the vaccine's effectiveness.
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Currently, SARS-CoV-2 spike receptor-binding-domain (RBD)-based vaccines are considered one of the most effective weapons against COVID-19. During the first step of assessing vaccine immunogenicity, a mouse model is often used. In this paper, we tested the use of five experimental animals (mice, hamsters, rabbits, ferrets, and chickens) for RBD immunogenicity assessments.

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HIV-1 env-pseudoviruses are a useful tool in the search for antiviral drugs (entry inhibitors) and evaluation of the efficacy of HIV-1 vaccines. Given the high genetic variability of HIV-1, it is necessary to regularly update the panels of pseudoviruses in accordance with the emergence of new strains. Based on genetic variants of HIV-1 circulating in the regions of the Siberian Federal District, 13 HIV-1 env-pseudoviruses of recombinant form CRF63_02A and subtype A6 were obtained.

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Article Synopsis
  • HIV infection continues to pose significant challenges to global healthcare systems, necessitating various counteractive measures, including education on prevention, testing, and treatment.
  • Effective prevention strategies include educational campaigns, protected sex practices, and pre-exposure prophylaxis for at-risk populations, while timely testing and antiretroviral therapy play crucial roles when individuals test positive.
  • Research aims to develop new pharmaceutical agents and HIV-1 vaccines, focusing on improved methods for efficacy assessment, with pseudoviruses serving as a safer and more efficient alternative to traditional viral isolates for analyzing neutralizing activity.
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Despite the fact that a range of vaccines against COVID-19 have already been created and are used for mass vaccination, the development of effective, safe, technological, and affordable vaccines continues. We have designed a vaccine that combines the recombinant protein and DNA vaccine approaches in a self-assembled particle. The receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 was conjugated to polyglucin:spermidine and mixed with DNA vaccine (pVAXrbd), which led to the formation of particles of combined coronavirus vaccine (CCV-RBD) that contain the DNA vaccine inside and RBD protein on the surface.

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The receptor-binding domain (RBD) of the protein S SARS-CoV-2 is considered to be one of the appealing targets for developing a vaccine against COVID-19. The choice of an expression system is essential when developing subunit vaccines, as it ensures the effective synthesis of the correctly folded target protein, and maintains its antigenic and immunogenic properties. Here, we describe the production of a recombinant RBD protein using prokaryotic (pRBD) and mammalian (mRBD) expression systems, and compare the immunogenicity of prokaryotic and mammalian-expressed RBD using a BALB/c mice model.

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When developing drugs against SARS-CoV-2, it is important to consider the characteristics of patients with different co-morbidities. People infected with HIV-1 are a particularly vulnerable group, as they may be at a higher risk than the general population of contracting COVID-19 with clinical complications. For such patients, drugs with a broad spectrum of antiviral activity are of paramount importance.

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