A TLR4-derived non-cytotoxic, self-assembling peptide functions as a vaccine adjuvant in mice
| Autor: | Shailja Misra Bhattacharya, Anshika Tandon, Mohd Sayeed, Mohammad Imran Siddiqi, Sabahuddin Ahmad, Munesh Kumar Harioudh, Kalyan Mitra, Jimut Kanti Ghosh, Tayyaba Afshan, Manisha Pathak |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Ovalbumin medicine.medical_treatment T cell CD14 Immunology Lymphocyte Antigen 96 Molecular Dynamics Simulation 010402 general chemistry 01 natural sciences Biochemistry Cell Line 03 medical and health sciences Mice Immune system Adjuvants Immunologic medicine Cytotoxic T cell Animals Humans Amino Acid Sequence Receptor Protein Structure Quaternary Molecular Biology Brugia malayi Vaccines biology Chemistry Cell Biology Peptide Fragments 0104 chemical sciences Molecular Docking Simulation Toll-Like Receptor 4 030104 developmental biology medicine.anatomical_structure Cancer research biology.protein Immunization Antibody Protein Multimerization Adjuvant |
| Zdroj: | The Journal of biological chemistry. 293(51) |
| ISSN: | 1083-351X |
| Popis: | Vaccination is devised/formulated to stimulate specific and prolonged immune responses for long-term protection against infection or disease. A vaccine component, namely adjuvant, enhances antigen recognition by the host immune system and thereby stimulates its cellular and adaptive responses. Especially synthetic Toll-like receptor (TLR) agonists having self-assembling properties are considered as good candidates for adjuvant development. Here, a human TLR4-derived 20-residue peptide (TR-433), present in the dimerization interface of the TLR4–myeloid differentiation protein-2 (MD2) complex, displayed self-assembly and adopted a nanostructure. Both in vitro studies and in vivo experiments in mice indicated that TR-433 is nontoxic. TR-433 induced pro-inflammatory responses in THP-1 monocytes and HEK293T cells that were transiently transfected with TLR4/CD14/MD2 and also in BALB/c mice. In light of the self-assembly and pro-inflammatory properties of TR-433, we immunized with a mixture of TR-433 and either ovalbumin or filarial antigen trehalose-6-phosphate phosphatase (TPP). A significant amount of IgG titers was produced, suggesting adjuvanting capability of TR-433 that was comparable with that of Freund's complete adjuvant (FCA) and appreciably higher than that of alum. We found that TR-433 preferentially activates type 1 helper T cell (T(h)1) response rather than type 2 helper T cell (T(h)2) response. To our knowledge, this is the first report on the identification of a short TLR4-derived peptide that possesses both self-assembling and pro-inflammatory properties and has significant efficacy as an adjuvant, capable of activating cellular responses in mice. These results indicate that TR-433 possesses significant potential for development as a new adjuvant in therapeutic application. |
| Databáze: | OpenAIRE |
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