Adjuvant Properties of Cytokines in Vaccination (Review)

Алпатова, Н. А.; Авдеева, Ж И; Никитина, Т Н; Медуницын, Н. В.

doi:10.1007/s11094-020-02111-3

Cited by 7 publications

(4 citation statements)

References 50 publications

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“…However, additional strategies are introduced to improve the immune response and serocon-version rates in vaccine recipients, especially in immune-compromised individuals 2 . Therefore, to enhance the immune response to vaccines, cytokines have been considered as adjuvant for their efficiency and safety 3 .…”

Section: Introductionmentioning

confidence: 99%

Transient Co-Expression of Bioactive Murine Interferon-Gamma and HBsAg in Tobacco and Lettuce Leaves

Mohammadzadeh,

Amiri,

Ehsani

2023

AJMB

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Background: The synchronous expression of antigen and adjuvant proteins in plant hosts presents an intriguing potential for vaccine production and the enhancement of appropriate immune responses. In this study, we examined the expression of bioactive murine interferon-gamma (mIFN-γ) along with HBsAg in tobacco and lettuce leaves aimed to further perform the analysis of immune responses in the mouse model. Methods: Monocistronic and bicistronic cassettes, carrying genes encoding mIFN-γ and HBsAg in various orders, were constructed. These cassettes were placed under the control of the 35S CaMV promoter and included the 5ʹ leader sequence of Tobacco Ech Virus (TEV). Through Agrobacterium infiltration, the cassettes were transferred into plant leaves. The concentration of mIFN-γ in different constructs and HBsAg was tested by ELISA. Murine IFN-γ was characterized through Western blotting, and its bioactivity was evaluated by assessing the up-regulation of MHC class II in macrophages derived from mouse bone marrow. Results: Extracts of agroinfiltrated leaves contained recombinant mIFN-γ and HBsAg proteins at about 14 unit/mg and 50 ng/mg of soluble protein, respectively. Subsequently, mIFN-γ was purified from the plant extract and its ability to up-regulate MHC class II in mouse bone marrow-derived macrophages was confirmed by immunofluorescence. Conclusion: The co-expression of recombinant HBsAg and mIFN-γ using TEV 5ʹ leader-based cassettes in tobacco and lettuce leaves produced both proteins with active mIFN-γ in different concentrations. The attractive utility and feasibility of using plant transient co-expression systems aimed to co-delivery of vaccine antigen and appropriate cytokine to elicit immune response for different applications.

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Section: Introductionmentioning

confidence: 99%

Transient Co-Expression of Bioactive Murine Interferon-Gamma and HBsAg in Tobacco and Lettuce Leaves

Mohammadzadeh,

Amiri,

Ehsani

2023

AJMB

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“…The relevance of the search for new vaccine adjuvants is growing along with the increase in the number of new vaccine preparations, especially those developed on the basis of proteins (subunit or peptide vaccines) or nucleic acids (RNA-, DNA-vaccines). Some cytokines are known to exert adjuvant properties [1,14], which allows them to be conside red as promising adjuvants of current vaccines.…”

Section: Introductionmentioning

confidence: 99%

“…Preventive vaccines based on GM-CSF elicited strong antitumor and antiviral immune responses in preclinical experiments [1,10,14]. However, in clinical studies, these effects were not always reproduced, moreover, at times they contradicted the…”

Section: Introductionmentioning

confidence: 99%

Study of the adjuvant properties of preparations containing recombinant human granulocyte-macrophage colony stimulating factor

et al. 2023

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The relevance of the search for new vaccine adjuvants is growing along with the increase in the number of current vaccine preparations, especially those developed on the basis of proteins. Some cytokines are known to exert adjuvant properties. The present work is devoted to the study of adjuvant activity of recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF) and constructs based on it. Earlier, we developed a technology for isolation and purification of GM-CSF from the E. coli SG20050/p280_2GM producer strain, as well as a technology for conjugating polyglucin:spermidine complexes with rhGM-CSF. Double-stranded RNA was used to obtain molecular constructs on the basis of rhGM-CSF conjugate. To assemble constructs, the ratio of the components was calculated for one dose of the preparation to contain 5-40 mg of rhGM-CSF and 100 mg of double-stranded RNA. The effectiveness of the formation of molecular constructs was evaluated by dsRNA electrophoretic mobility shift in a 1% agarose gel. The effectiveness of the resulting adjuvants was determined in ELISA assays by measuring the titers of specific antibodies in mouse sera against ovalbumin or recombinant receptor-binding domain of the surface S protein of the severe acute respiratory syndrome coronavirus 2 (Delta variant (B.1.617.2). The experiments were carried out in 100 male BALB/c mice weighing 16-18 g. Mice were immunized twice, with a 14-day interval, by intramuscular injection of 200 mL per animal. Recombinant receptor-binding domain of the surface protein of SARS-CoV-2 was administered at a dose of 50 mg/animal, ovalbumin – at two doses – 1 mg or 5 mg/animal. Corresponding antigen was used as a positive control, a saline solution – as a negative control. It was shown that the maximum effect was achieved by immunization with a construct based on double-stranded RNA and rhGM-CSF conjugated to polyglucin-spermidine. The use of a conjugate without double-stranded RNA as an adjuvant also improved humoral response. The use of native rhGM-CSF did not increase the titers of specific antibodies. Thus, it was found that rhGM-CSF being a part of a polysaccharide conjugate or a molecular construct exerted an ability to enhance the humoral immune response to protein antigens.

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“…Recent studies, carried out on animal tumor models, show that different cytokines, including GM-CSF, IL-7, IL-12, IL-15, IL-18 and IL-21, are also able to limit tumor growth [9]. This important role in the regulation of the immune response outlines a potential use of cytokines as immuno-adjuvants for vaccination [10]. In fact, the addition of cytokines, as recombinant proteins or as cytokine-coded plasmids, causes immunomodulation or, more simply, an enhanced immune response to vaccines [6].…”

Section: Introductionmentioning

confidence: 99%

Therapeutic and Prophylactic Use of Oral, Low-Dose IFNs in Species of Veterinary Interest: Back to the Future

Frazzini

Riva

Amadori³

2021

Veterinary Sciences

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Cytokines are important molecules that orchestrate the immune response. Given their role, cytokines have been explored as drugs in immunotherapy in the fight against different pathological conditions such as bacterial and viral infections, autoimmune diseases, transplantation and cancer. One of the problems related to their administration consists in the definition of the correct dose to avoid severe side effects. In the 70s and 80s different studies demonstrated the efficacy of cytokines in veterinary medicine, but soon the investigations were abandoned in favor of more profitable drugs such as antibiotics. Recently, the World Health Organization has deeply discouraged the use of antibiotics in order to reduce the spread of multi-drug resistant microorganisms. In this respect, the use of cytokines to prevent or ameliorate infectious diseases has been highlighted, and several studies show the potential of their use in therapy and prophylaxis also in the veterinary field. In this review we aim to review the principles of cytokine treatments, mainly IFNs, and to update the experiences encountered in animals.

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Adjuvant Properties of Cytokines in Vaccination (Review)

Cited by 7 publications

References 50 publications

Transient Co-Expression of Bioactive Murine Interferon-Gamma and HBsAg in Tobacco and Lettuce Leaves

Transient Co-Expression of Bioactive Murine Interferon-Gamma and HBsAg in Tobacco and Lettuce Leaves

Study of the adjuvant properties of preparations containing recombinant human granulocyte-macrophage colony stimulating factor

Therapeutic and Prophylactic Use of Oral, Low-Dose IFNs in Species of Veterinary Interest: Back to the Future

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