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Title: Size-dependent immunogenicity: therapeutic and protective properties of nano-vaccines against tumors.
Austin Authors: Fifis, Theodora;Gamvrellis, Anita;Crimeen-Irwin, Blessing;Pietersz, Geoffrey A;Li, Jie;Mottram, Patricia L;McKenzie, Ian F C;Plebanski, Magdalena
Affiliation: Austin Research Institute, Austin Hospital, Heidelberg, Victoria, Australia
Issue Date: 1-Sep-2004
Publication information: Journal of Immunology (baltimore, Md. : 1950); 173(5): 3148-54
Abstract: Infection can protect against subsequent disease by induction of both humoral and cellular immunity, but inert protein-based vaccines are not as effective. In this study, we present a new vaccine design, with Ag covalently conjugated to solid core nano-beads of narrowly defined size (0.04-0.05 microm) that localize to dendritic cells (DEC205(+) CD40(+), CD86(+)) in draining lymph nodes, inducing high levels of IFN-gamma production (CD8 T cells: precursor frequencies 1/5000 to 1/1000) and high Ab titers in mice. Conjugation of Ag to these nano-beads induced responses that were significantly higher (2- to 10-fold) than those elicited by other bead sizes, and higher than a range of currently used adjuvants (alum, QuilA, monophosphoryl lipid A). Responses were comparable to CFA/IFA immunization for Abs and ex vivo peptide-pulsed dendritic cell immunization for CD8 T cells. A single dose of Ag-conjugated beads protected mice from tumors in two different model challenges and caused rapid clearance of established tumors in mice. Thus, a range of Ags conjugated to nano-beads was effective as immunogens in both therapeutic and prophylactic scenarios.
Gov't Doc #: 15322175
Journal: Journal of Immunology (Baltimore, Md. : 1950)
Type: Journal Article
Subjects: Adjuvants, Immunologic.pharmacology
Cancer Vaccines.immunology.pharmacology
Disease Models, Animal
Neoplasms.drug therapy.immunology.prevention & control
Appears in Collections:Journal articles

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