NSOM‐ and AFM‐based nanotechnology elucidates nano‐structural and atomic‐force features of a Y. pestis V immunogen‐containing particle vaccine capable of eliciting robust response |
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Authors: | Gucheng Zeng Jianbo Chen Liyun Zhong Richard Wang Lifang Jiang Jiye Cai Lin Yan Dan Huang Crystal Y Chen Zheng W Chen Professor |
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Institution: | 1. Department of Microbiology and Immunology, University of Illinois, Chicago, IL, USA;2. Department of Microbiology, Zhongshan Medical College, Sun Yat‐Sen University, Guangzhou, P. R. China;3. Department of Chemistry and Institute for Nano‐Chemistry, Jinan University, Guangzhou, P. R. China |
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Abstract: | It is postulated that unique nanoscale proteomic features of immunogen on vaccine particles may determine immunogen‐packing density, stability, specificity, and pH‐sensitivity on the vaccine particle surface and thus impact the vaccine‐elicited immune responses. To test this presumption, we employed near‐filed scanning optical microscopy (NSOM)‐ and atomic force microscopy (AFM)‐based nanotechnology to study nano‐structural and single‐molecule force bases of Yersinia pestis (Y. pestis) V immunogen fused with protein anchor (V‐PA) loaded on gram positive enhancer matrix (GEM) vaccine particles. Surprisingly, the single‐molecule sensitive NSOM revealed that ~90% of V‐PA immunogen molecules were packed as high‐density nanoclusters on GEM particle. AFM‐based single‐molecule force analyses indicated a highly stable and specific binding between V‐PA and GEM at the physiological pH. In contrast, this specific binding was mostly abrogated at the acidic pH equivalent to the biochemical pH in phagolysosomes of antigen‐presenting‐cells in which immunogen protein is processed for antigen presentation. Intranasal mucosal vaccination of mice with such immunogen loaded on vaccine particles elicited robust antigen‐specific immune response. This study indicated that high‐density, high‐stability, specific, and immunological pH‐responsive loading of immunogen nanoclusters on vaccine particles could readily be presented to the immune system for induction of strong antigen‐specific immune responses. |
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Keywords: | AFM Nanobiotechnology Nanoimmunology Nanoproteomics NSOM |
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