Size-Dependent Immunogenicity: Therapeutic and Protective Properties of Nano-Vaccines against Tumors

TLDR

Infection can protect against subsequent disease through both humoral and cellular immunity, yet inert protein‑based vaccines are not as effective. The study introduces a vaccine in which antigen is covalently attached to 0.04–0.05 µm solid‑core nano‑beads that target dendritic cells in draining lymph nodes, eliciting strong IFN‑γ production and high antibody titers in mice. Conjugation to these nano‑beads generated 2‑ to 10‑fold higher immune responses than other bead sizes and standard adjuvants, matched CFA/IFA for antibodies and peptide‑pulsed dendritic‑cell immunization for CD8 T cells, and a single dose protected mice from tumors and cleared established tumors, demonstrating both therapeutic and prophylactic efficacy.

Abstract

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 μm) that localize to dendritic cells (DEC205+ CD40+, CD86+) in draining lymph nodes, inducing high levels of IFN-γ 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.