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Conjugation of TLR7 and TLR7/8 agonists onto weak protein antigen via versatile oxime ligation for enhanced vaccine efficacy.
Zhang, Ru-Yan; Wen, Yu; He, Chen-Bin; Zhou, Shi-Hao; Wu, Ye-Hui; Wang, En-Yang; Feng, Ran-Ran; Ding, Dong; Du, Jing-Jing; Gao, Xiao-Fei; Guo, Jun.
Afiliación
  • Zhang RY; National Key Laboratory of Green Pesticide, International Joint Research Center for Intelligent Biosensing Technology and Health, College of Chemistry, Central China Normal University, Wuhan 430079, China; Hubei Key Laboratory of Kidney Disease Pathogenesis and Intervention, College of Medicine, Hub
  • Wen Y; National Key Laboratory of Green Pesticide, International Joint Research Center for Intelligent Biosensing Technology and Health, College of Chemistry, Central China Normal University, Wuhan 430079, China.
  • He CB; National Key Laboratory of Green Pesticide, International Joint Research Center for Intelligent Biosensing Technology and Health, College of Chemistry, Central China Normal University, Wuhan 430079, China.
  • Zhou SH; National Key Laboratory of Green Pesticide, International Joint Research Center for Intelligent Biosensing Technology and Health, College of Chemistry, Central China Normal University, Wuhan 430079, China.
  • Wu YH; National Key Laboratory of Green Pesticide, International Joint Research Center for Intelligent Biosensing Technology and Health, College of Chemistry, Central China Normal University, Wuhan 430079, China.
  • Wang EY; National Key Laboratory of Green Pesticide, International Joint Research Center for Intelligent Biosensing Technology and Health, College of Chemistry, Central China Normal University, Wuhan 430079, China.
  • Feng RR; National Key Laboratory of Green Pesticide, International Joint Research Center for Intelligent Biosensing Technology and Health, College of Chemistry, Central China Normal University, Wuhan 430079, China.
  • Ding D; National Key Laboratory of Green Pesticide, International Joint Research Center for Intelligent Biosensing Technology and Health, College of Chemistry, Central China Normal University, Wuhan 430079, China.
  • Du JJ; Hubei Key Laboratory of Kidney Disease Pathogenesis and Intervention, College of Medicine, Hubei Polytechnic University, Huangshi 435003, China.
  • Gao XF; Jiangxi Key Laboratory for Mass Spectrometry and Instrumentation, School of Chemistry and Materials Science, East China University of Technology, Nanchang 330013, China.
  • Guo J; National Key Laboratory of Green Pesticide, International Joint Research Center for Intelligent Biosensing Technology and Health, College of Chemistry, Central China Normal University, Wuhan 430079, China. Electronic address: jguo@ccnu.edu.cn.
Int J Biol Macromol ; 278(Pt 1): 134620, 2024 Oct.
Article en En | MEDLINE | ID: mdl-39127274
ABSTRACT
Protein-based subunit vaccines are weakly immunogenic, and developing self-adjuvanting vaccines with adjuvant conjugated to antigen is a promising approach for generating optimal immune responses. Here, we report a novel adjuvant-protein conjugate vaccine based on versatile oxime ligation technique. Firstly, the adjuvant properties of a series of TLR7 and TLR7/8 small molecule agonists in self-adjuvanting vaccines were systematically compared by coupling them to proteins in consistent ratio via p-carboxybenzaldehyde (p-CBA) for the first time. All conjugate vaccines induced cytokine secretion in murine and human macrophages in vitro, and promoted specific antibody production in vivo. Notably, a conjugate containing imidazoquinoline TLR7/8 agonist (TLR7/8a1) showed the greatest enhancement in Th1/2 balanced antibody response. To minimize the interference with the protein antigenic integrity, we further developed a systematic glycoconjugation strategy to conjugate this TLR7/8a1 onto the glycan chains of SARS-CoV-2 S1 glycoprotein via oxime ligation, in which S1 containing different numbers of aldehyde groups were obtained by differential periodate oxidation. The resulting TLR7/8a1-S1 conjugate triggered a potent humoral and cellular immunity in vivo. Together these data demonstrate the promise of these TLR7 and TLR7/8 agonists as effective built-in adjuvants, and the versatile oxime ligation strategy might broaden potential applications in designing different conjugate vaccines.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Oximas / Adyuvantes Inmunológicos / Receptor Toll-Like 7 / Receptor Toll-Like 8 Límite: Animals / Female / Humans Idioma: En Revista: Int J Biol Macromol Año: 2024 Tipo del documento: Article Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Oximas / Adyuvantes Inmunológicos / Receptor Toll-Like 7 / Receptor Toll-Like 8 Límite: Animals / Female / Humans Idioma: En Revista: Int J Biol Macromol Año: 2024 Tipo del documento: Article Pais de publicación: Países Bajos