Size-dependent immunogenicity: therapeutic and protective properties of nano-vaccines against tumors

J Immunol. 2004 Sep 1;173(5):3148-54. doi: 10.4049/jimmunol.173.5.3148.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adjuvants, Immunologic / pharmacology
  • Animals
  • Antigens / immunology
  • Cancer Vaccines / immunology*
  • Cancer Vaccines / pharmacology
  • Disease Models, Animal
  • Mice
  • Nanotechnology*
  • Nanotubes
  • Neoplasms / drug therapy
  • Neoplasms / immunology
  • Neoplasms / prevention & control*

Substances

  • Adjuvants, Immunologic
  • Antigens
  • Cancer Vaccines