Methods of effective conjugation of antigens to nanoparticles as non-inflammatory vaccine carriers

Xiang, S, Wilson, K, Day, S, Fuchsberger, M and Plebanski, M 2013, 'Methods of effective conjugation of antigens to nanoparticles as non-inflammatory vaccine carriers', Methods, vol. 60, no. 3, pp. 232-241.


Document type: Journal Article
Collection: Journal Articles

Title Methods of effective conjugation of antigens to nanoparticles as non-inflammatory vaccine carriers
Author(s) Xiang, S
Wilson, K
Day, S
Fuchsberger, M
Plebanski, M
Year 2013
Journal name Methods
Volume number 60
Issue number 3
Start page 232
End page 241
Total pages 10
Publisher Academic Press
Abstract It has recently become clear that nanoparticle size is a major determinant for how antigen presenting cells (APCs), and specifically dendritic cells (DC) recognize and handle particles, and hence a critical parameter for the formulation of particulate vaccines that aim to induce immunity by targeting DC. Our previous studies in mice and sheep have shown polystyrene nanoparticles of 4050 nm (PSNPs) with covalently bound antigen offer a new class of vaccines, which contain only 2 elements, antigen and particle, and no added inflammatory stimuli, but evoke very potent combined CD8 T cell and antibody responses. Herein we have optimized the methods for antigen conjugation to PSNPs to controllably promote a single antigen (protein or peptide) layer coating on the nanoparticle. Surprisingly, these nanovaccines not only continued to induce high levels of CD8 T cells in vivo, but were further more potent antibody inducers than nanoparticles containing multiple antigen layers. Addressing the issue of antigen loading on PSNPs, we found an optimal range, above or below which immunogenicity is changed either for antibodies or CD8 T cells. The mechanism behind the induction of high levels of CD8 T cells was further explored by assessing the DC subset that takes up the PSNPs in vivo, and these were found to be preferentially CD8+ CD11c+ DC in the lymph node draining the injection site. Since the levels of induced antibodies were highly elevated, and CD8+ DC do not traditionally induce antibodies, we further sought to find if, despite no detectable inflammation at the injection site, the PSNPs may perhaps induce inflammatory cytokines locally in the lymph node after injection, or systemically in sera, resulting in an adjuvant effect. The initial findings presented herein show no detectable induction of the key inflammatory cytokines such as TNF-α, IL-1 or IL-6, suggesting a novel non-inflammatory adjuvant mechanism.
Subject Immunology not elsewhere classified
Keyword(s) Antibody
Antigen load
CD8
Inflammation
Nanoparticle
Vaccine
DOI - identifier 10.1016/j.ymeth.2013.03.036
Copyright notice © 2013 Elsevier Inc.
ISSN 1046-2023
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