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.
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 approximately 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.
Zeng
Gucheng
G
Department of Microbiology and Immunology, University of Illinois, Chicago, IL 60612, USA.
Chen
Jianbo
J
Zhong
Liyun
L
Wang
Richard
R
Jiang
Lifang
L
Cai
Jiye
J
Yan
Lin
L
Huang
Dan
D
Chen
Crystal Y
CY
Chen
Zheng W
ZW
D000281:Administration, Intranasal; D000818:Animals; D000942:Antigens, Bacterial / Q000737:chemistry* / Q000276:immunology*; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology*; D051379:Mice; D018625:Microscopy, Atomic Force; D018613:Microscopy, Confocal; D049329:Nanostructures / Q000737:chemistry*; D036103:Nanotechnology / Q000379:methods*; D040901:Proteomics; D045663:Quantum Dots; D014611:Vaccination; D015010:Yersinia pestis / Q000276:immunology*
D000942:Antigens, Bacterial; D001428:Bacterial Vaccines