Size-dependent immunogenicity: therapeutic and protective properties of nano-vaccines against tumors.
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.
Fifis
Theodora
T
Austin Research Institute, Austin Hospital, Heidelberg, Victoria, Australia.
Gamvrellis
Anita
A
Crimeen-Irwin
Blessing
B
Pietersz
Geoffrey A
GA
Li
Jie
J
Mottram
Patricia L
PL
McKenzie
Ian F C
IF
Plebanski
Magdalena
M
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D000941:Antigens / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology* / Q000494:pharmacology; D004195:Disease Models, Animal; D051379:Mice; D036103:Nanotechnology; D043942:Nanotubes; D009369:Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000517:prevention & control*
D000276:Adjuvants, Immunologic; D000941:Antigens; D019496:Cancer Vaccines