HBD-3 induces NK cell activation, IFN-γ secretion and mDC dependent cytolytic function

Judge, Chelsey J.; Reyes-Avilés, Elane; Conry, Sara J.; Sieg, Scott; Feng, Zhihui; Weinberg, Aaron; Anthony, Donald D.

doi:10.1016/j.cellimm.2015.06.004

Cited by 17 publications

(18 citation statements)

References 36 publications

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“…94 It activates APCs via TLR1 and TLR2 95 and induces IL-22, 96 TGF-α 97,98 and IFN-γ. 99,100 It has been implicated in the chemotaxis of immature DCs and T cells via its interaction with chemokine receptor 6 (CCR6) and the chemotaxis of monocytes via interaction with CCR2, 101 As well as this peptide activates natural killer (NK), promotes and activates myeloid DCs directly and dependent NK cells activity. 95,100 To link different pieces of the vaccine, a repeated of a dipeptide linker of LE was used.…”

Section: Discussionmentioning

confidence: 99%

<p>Design an Efficient Multi-Epitope Peptide Vaccine Candidate Against SARS-CoV-2: An in silico Analysis</p>

Yazdani¹,

Rafiei²,

Yazdani³

et al. 2020

IDR

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Background: To date, no specific vaccine or drug has been proven to be effective against SARS-CoV-2 infection. Therefore, we implemented an immunoinformatic approach to design an efficient multi-epitopes vaccine against SARS-CoV-2. Results: The designed-vaccine construct consists of several immunodominant epitopes from structural proteins of spike, nucleocapsid, membrane, and envelope. These peptides promote cellular and humoral immunity and interferon-gamma responses. Also, these epitopes have a high antigenic capacity and are not likely to cause allergies. To enhance the vaccine immunogenicity, we used three potent adjuvants: Flagellin of Salmonella enterica subsp. enterica serovar Dublin, a driven peptide from high mobility group box 1 as HP-91, and human beta-defensin 3 protein. The physicochemical and immunological properties of the vaccine structure were evaluated. The tertiary structure of the vaccine protein was predicted and refined by Phyre2 and Galaxi refine and validated using RAMPAGE and ERRAT. Results of ElliPro showed 246 sresidues from vaccine might be conformational B-cell epitopes. Docking of the vaccine with toll-like receptors (TLR) 3, 5, 8, and angiotensinconverting enzyme 2 approved an appropriate interaction between the vaccine and receptors. Prediction of mRNA secondary structure and in silico cloning demonstrated that the vaccine can be efficiently expressed in Escherichia coli. Conclusion: Our results demonstrated that the multi-epitope vaccine might be potentially antigenic and induce humoral and cellular immune responses against SARS-CoV-2. This vaccine can interact appropriately with the TLR3, 5, and 8. Also, it has a high-quality structure and suitable characteristics such as high stability and potential for expression in Escherichia coli .

show abstract

Section: Discussionmentioning

confidence: 99%

<p>Design an Efficient Multi-Epitope Peptide Vaccine Candidate Against SARS-CoV-2: An in silico Analysis</p>

Yazdani¹,

Rafiei²,

Yazdani³

et al. 2020

IDR

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“…This peptide blocks viral fusion using creating a protective barricade of immobilized surface proteins[88]. It activates APCs via TLR1 and TLR2[89] and induces IL-22[90], TGF-α[91, 92] and IFN-γ[93, 94]. It has been implicated in the chemotaxis of immature DCs and T cells via its interaction with chemokine receptor 6 (CCR6) and the chemotaxis of monocytes via interaction with CCR2[95], As well as this peptide activates NK cells, promotes and activates myeloid DCs directly and dependent Natural killer (NK) activity[89, 94].…”

Section: Discussionmentioning

confidence: 99%

Design an efficient multi-epitope peptide vaccine candidate against SARS-CoV-2: An in silico analysis

Yazdani

Rafiei

Yazdani

et al. 2020

Preprint

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Background: To date, no specific vaccine or drug has been proven to be effective for SARS-CoV-2 infection. Therefore, we implemented immunoinformatics approach to design an efficient multi-epitopes vaccine against SARS-CoV-2.Results: The designed vaccine construct has several immunodominant epitopes from structural proteins of Spike, Nucleocapsid, Membrane and Envelope. These peptides promote cellular and humoral immunity and Interferon gamma responses. In addition, these epitopes have antigenicity ability and no allergenicity probability. To enhance the vaccine immunogenicity, we used three potent adjuvants; Flagellin, a driven peptide from high mobility group box 1 as HP-91 and human beta defensin 3 protein. The physicochemical and immunological properties of the vaccine structure were evaluated. Tertiary structure of the vaccine protein was predicted and refined by I-Tasser and galaxi refine and validated using Rampage and ERRAT. Results of Ellipro showed 242 residues from vaccine might be conformational B cell epitopes. Docking of vaccine with Toll-Like Receptors 3, 5 and 8 proved an appropriate interaction between the vaccine and receptor proteins. In silico cloning demonstrated that the vaccine can be efficiently expressed in Escherichia coli.Conclusions: The designed multi epitope vaccine is potentially antigenic in nature and has the ability to induce humoral and cellular immune responses against SARS-CoV-2. This vaccine can interact appropriately with the TLR3, 5, and 8. Also, this vaccine has high quality structure and suitable characteristics such as high stability and potential for expression in Escherichia coli.

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“…However, hBD3 has no effect on IL-10 induction by Pam3CSK4, indicating that hBD3 does not complete for the binding of Pam 3 CSK 4 to TLR1/2 receptors [103]. hBD3 induces expression of stimulatory receptor CD69 on NK cells through TLR1/TLR2, and this induction is facilitated by CCR2 [104]. hBD3 induces NK cell-mediated IFNγ secretion and promotes mDC-dependent NK cell cytotoxic activity [104]…”

Section: Human β-Defensinsmentioning

confidence: 99%

Multifaceted immune functions of human defensins and underlying mechanisms

Fruitwala

El-Naccache

Chang

2019

Seminars in Cell & Developmental Biology

125

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Defensins have been long recognized as natural antimicrobial peptides, but they also possess diverse and versatile immune functions. Defensins can both induce inflammation and suppress inflammatory responses by acting on specific cells through distinct mechanisms. Defensins can also modulate the immune response by forming a complex with cellular molecules including proteins, nucleic acids, and carbohydrates. The mechanisms of defensin-mediated immune modulation appear to be cell-type and context specific. Because the levels of human defensins are often altered in response to infection or disease states, suggesting their clinical relevance, this review summarizes the complex immune functions of human defensins and their underlying mechanisms of action, which have implications for the development of new therapeutics.

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HBD-3 induces NK cell activation, IFN-γ secretion and mDC dependent cytolytic function

Cited by 17 publications

References 36 publications

<p>Design an Efficient Multi-Epitope Peptide Vaccine Candidate Against SARS-CoV-2: An in silico Analysis</p>

<p>Design an Efficient Multi-Epitope Peptide Vaccine Candidate Against SARS-CoV-2: An in silico Analysis</p>

Design an efficient multi-epitope peptide vaccine candidate against SARS-CoV-2: An in silico analysis

Multifaceted immune functions of human defensins and underlying mechanisms

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