دورية أكاديمية
Chimeric NOD2 Mincle Agonists as Vaccine Adjuvants.
| العنوان: | Chimeric NOD2 Mincle Agonists as Vaccine Adjuvants. |
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| المؤلفون: | Dangerfield EM; School of Chemical and Physical Sciences, Victoria University of Wellington, PO Box 600, Wellington 6140, New Zealand.; Centre for Biodiscovery, Victoria University of Wellington, PO Box 600, Wellington 6140, New Zealand., Ishizuka S; Department of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan.; Laboratory of Molecular Immunology, Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan., Kodar K; School of Chemical and Physical Sciences, Victoria University of Wellington, PO Box 600, Wellington 6140, New Zealand.; Centre for Biodiscovery, Victoria University of Wellington, PO Box 600, Wellington 6140, New Zealand., Yamasaki S; Department of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan.; Laboratory of Molecular Immunology, Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan.; Division of Molecular Immunology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Fukuoka 812-8582, Japan.; Division of Molecular Immunology, Medical Mycology Research Center, Chiba University, Chiba, 260-8673, Japan., Timmer MSM; School of Chemical and Physical Sciences, Victoria University of Wellington, PO Box 600, Wellington 6140, New Zealand.; Centre for Biodiscovery, Victoria University of Wellington, PO Box 600, Wellington 6140, New Zealand., Stocker BL; School of Chemical and Physical Sciences, Victoria University of Wellington, PO Box 600, Wellington 6140, New Zealand.; Centre for Biodiscovery, Victoria University of Wellington, PO Box 600, Wellington 6140, New Zealand. |
| المصدر: | Journal of medicinal chemistry [J Med Chem] 2024 Apr 11; Vol. 67 (7), pp. 5373-5390. Date of Electronic Publication: 2024 Mar 20. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Chemical Society Country of Publication: United States NLM ID: 9716531 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1520-4804 (Electronic) Linking ISSN: 00222623 NLM ISO Abbreviation: J Med Chem Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Washington Dc : American Chemical Society Original Publication: [Easton, Pa.] : American Chemical Society, [c1963- |
| مواضيع طبية MeSH: | Adjuvants, Vaccine* , Pathogen-Associated Molecular Pattern Molecules*, Adjuvants, Immunologic/pharmacology ; Adjuvants, Immunologic/chemistry ; Immunity, Cellular ; Cytokines ; Antigens ; Receptors, Immunologic ; Lectins, C-Type |
| مستخلص: | There is a need for improved vaccine adjuvants to augment vaccine efficacy. One way to address this is by targeting multiple immune cell pathogen recognition receptors (PRRs) using chimeric pathogen-associated molecular patterns (PAMPs). Conjugation of the PAMPs will ensure codelivery of the immunostimulatory molecules to the same cell, enhancing adjuvant activity. The macrophage inducible C-type lectin (Mincle) is a promising PRR for adjuvant development; however, no effective chimeric Mincle adjuvants have been prepared. We addressed this by synthesizing Mincle adjuvant conjugates, MDP-C18Brar and MDP-C18Brar-dilipid, which contain PAMPs recognized by Mincle and the nucleotide-binding oligomerization domain 2 (NOD2). The two PAMPs are joined by a pH-sensitive oxyamine linker which, upon acidification at lysosomal pH, hydrolyzed to release the NOD2 ligands. The conjugates elicited the production of Th1 and Th17 promoting cytokines in vitro , and when using OVA as a model antigen, exhibited enhanced T-cell-mediated immune responses and reduced toxicity in vivo , compared to the coadministration of the adjuvants. |
| المشرفين على المادة: | 0 (Adjuvants, Vaccine) 0 (Pathogen-Associated Molecular Pattern Molecules) 0 (Adjuvants, Immunologic) 0 (Cytokines) 0 (Antigens) 0 (Receptors, Immunologic) 0 (Lectins, C-Type) |
| تواريخ الأحداث: | Date Created: 20240320 Date Completed: 20240412 Latest Revision: 20240412 |
| رمز التحديث: | 20240412 |
| DOI: | 10.1021/acs.jmedchem.3c01840 |
| PMID: | 38507580 |
| قاعدة البيانات: | MEDLINE |
Find this issue from the American Chemical Society | تدمد: | 1520-4804 |
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| DOI: | 10.1021/acs.jmedchem.3c01840 |