Size-dependent immunogenicity: therapeutic and protective properties of nano-vaccines against tumors.
J Immunol
; 173(5): 3148-54, 2004 Sep 01.
Article
em En
| MEDLINE
| ID: mdl-15322175
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.
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Base de dados:
MEDLINE
Assunto principal:
Vacinas Anticâncer
/
Nanotecnologia
/
Neoplasias
Limite:
Animals
Idioma:
En
Ano de publicação:
2004
Tipo de documento:
Article