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Nanoparticle Size Influences Antigen Retention and Presentation in Lymph Node Follicles for Humoral Immunity.
Nano Lett 2019; 19(10):7226-7235NL

Abstract

Lymph node follicles capture and retain antigens to induce germinal centers and long-lived humoral immunity. However, control over antigen retention has been limited. Here we discovered that antigen conjugated to nanoparticle carriers of different sizes impacts the intralymph node transport and specific cell interaction. We found that follicular dendritic cell (FDC) networks determine the intralymph node follicle fate of these nanoparticles by clearing smaller ones (5-15 nm) within 48 h and retaining larger ones (50-100 nm) for over 5 weeks. The 50-100 nm-sized nanoparticles had 175-fold more delivery of antigen at the FDC dendrites, 5-fold enhanced humoral immune responses of germinal center B cell formation, and 5-fold more antigen-specific antibody production over 5-15 nm nanoparticles. Our results show that we can tune humoral immunity by simply manipulating the carrier size design to produce effectiveness of vaccines.

Authors+Show Affiliations

Institute of Biomaterials & Biomedical Engineering , University of Toronto , Toronto , Ontario M5S 3G9 , Canada. Terrence Donnelly Centre for Cellular & Biomolecular Research , University of Toronto , Toronto , Ontario M5S 3E1 , Canada.Institute of Biomaterials & Biomedical Engineering , University of Toronto , Toronto , Ontario M5S 3G9 , Canada. Terrence Donnelly Centre for Cellular & Biomolecular Research , University of Toronto , Toronto , Ontario M5S 3E1 , Canada.Institute of Biomaterials & Biomedical Engineering , University of Toronto , Toronto , Ontario M5S 3G9 , Canada. Terrence Donnelly Centre for Cellular & Biomolecular Research , University of Toronto , Toronto , Ontario M5S 3E1 , Canada.Institute of Biomaterials & Biomedical Engineering , University of Toronto , Toronto , Ontario M5S 3G9 , Canada. Terrence Donnelly Centre for Cellular & Biomolecular Research , University of Toronto , Toronto , Ontario M5S 3E1 , Canada. MD/PhD Program, Faculty of Medicine , University of Toronto , Toronto , Ontario M5S 1A8 , Canada.Institute of Biomaterials & Biomedical Engineering , University of Toronto , Toronto , Ontario M5S 3G9 , Canada. Terrence Donnelly Centre for Cellular & Biomolecular Research , University of Toronto , Toronto , Ontario M5S 3E1 , Canada.Institute of Biomaterials & Biomedical Engineering , University of Toronto , Toronto , Ontario M5S 3G9 , Canada. Terrence Donnelly Centre for Cellular & Biomolecular Research , University of Toronto , Toronto , Ontario M5S 3E1 , Canada.Institute of Biomaterials & Biomedical Engineering , University of Toronto , Toronto , Ontario M5S 3G9 , Canada. Terrence Donnelly Centre for Cellular & Biomolecular Research , University of Toronto , Toronto , Ontario M5S 3E1 , Canada. Department of Chemical Engineering & Applied Chemistry , University of Toronto , Toronto , Ontario M5S 3E5 , Canada. Department of Materials Science & Engineering , University of Toronto , Toronto , Ontario M5S 1A1 , Canada. Department of Chemistry , University of Toronto , Toronto , Ontario M5S 3H6 , Canada.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31508968

Citation

Zhang, Yi-Nan, et al. "Nanoparticle Size Influences Antigen Retention and Presentation in Lymph Node Follicles for Humoral Immunity." Nano Letters, vol. 19, no. 10, 2019, pp. 7226-7235.
Zhang YN, Lazarovits J, Poon W, et al. Nanoparticle Size Influences Antigen Retention and Presentation in Lymph Node Follicles for Humoral Immunity. Nano Lett. 2019;19(10):7226-7235.
Zhang, Y. N., Lazarovits, J., Poon, W., Ouyang, B., Nguyen, L. N. M., Kingston, B. R., & Chan, W. C. W. (2019). Nanoparticle Size Influences Antigen Retention and Presentation in Lymph Node Follicles for Humoral Immunity. Nano Letters, 19(10), pp. 7226-7235. doi:10.1021/acs.nanolett.9b02834.
Zhang YN, et al. Nanoparticle Size Influences Antigen Retention and Presentation in Lymph Node Follicles for Humoral Immunity. Nano Lett. 2019 Oct 9;19(10):7226-7235. PubMed PMID: 31508968.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Nanoparticle Size Influences Antigen Retention and Presentation in Lymph Node Follicles for Humoral Immunity. AU - Zhang,Yi-Nan, AU - Lazarovits,James, AU - Poon,Wilson, AU - Ouyang,Ben, AU - Nguyen,Luan N M, AU - Kingston,Benjamin R, AU - Chan,Warren C W, Y1 - 2019/09/17/ PY - 2019/9/12/pubmed PY - 2019/9/12/medline PY - 2019/9/12/entrez KW - Nanoparticle KW - antigen retention and presentation KW - complement KW - follicular dendritic cells KW - germinal centers KW - lymph node SP - 7226 EP - 7235 JF - Nano letters JO - Nano Lett. VL - 19 IS - 10 N2 - Lymph node follicles capture and retain antigens to induce germinal centers and long-lived humoral immunity. However, control over antigen retention has been limited. Here we discovered that antigen conjugated to nanoparticle carriers of different sizes impacts the intralymph node transport and specific cell interaction. We found that follicular dendritic cell (FDC) networks determine the intralymph node follicle fate of these nanoparticles by clearing smaller ones (5-15 nm) within 48 h and retaining larger ones (50-100 nm) for over 5 weeks. The 50-100 nm-sized nanoparticles had 175-fold more delivery of antigen at the FDC dendrites, 5-fold enhanced humoral immune responses of germinal center B cell formation, and 5-fold more antigen-specific antibody production over 5-15 nm nanoparticles. Our results show that we can tune humoral immunity by simply manipulating the carrier size design to produce effectiveness of vaccines. SN - 1530-6992 UR - https://www.unboundmedicine.com/medline/citation/31508968/Nanoparticle_size_influences_antigen_retention_and_presentation_in_lymph_node_follicles_for_humoral_immunity L2 - https://dx.doi.org/10.1021/acs.nanolett.9b02834 DB - PRIME DP - Unbound Medicine ER -