Covering Aluminum Oxide Nanoparticles with Biocompatible Materials to Efficiently Deliver Subunit Vaccines

Abstract

Subunit vaccines have advantages of good safety, minimal reactogenicity, and high specificity. However, subunit vaccines also show a crucial disadvantage of poor immunogenicity and, therefore, are often formulated with an adjuvant carrier to form a vaccine adjuvant-delivery system (VADS) to enhance their efficacies. Alums, the coarse aggregates of the insoluble aluminum salts, are the conventional adjuvants and have been widely used in clinical vaccines for a long time. Unfortunately, alums also show two main drawbacks of low potency in eliciting cellular immunity, and high reactogenicity to cause unwanted inflammations. Therefore, herein the phospholipid bilayer-coated aluminum oxide nanoparticles (PLANs) and the PEGylated PLANs (PEG-PLANs) were engineered as a VADS to overcome the drawbacks of both subunit vaccines and coarse alums, while synergizing their functions. In vitro experiments demonstrated that, unlike the micron-sized alums, the nanosized PLANs and PEG-PLANs loaded with model antigen of ovalbumin (OVA) showed a high safety profile and were able to promote APC (antigen-presenting cell) uptake and engender lysosome escape for enhancing the MHC (major histocompatibility complex)-I-antigen display. Subcutaneously administered to mice, PLANs and, especially, PEG-PLANs smoothly trafficked into the draining lymph nodes, wherein the densely clustered immune cells were activated in substantial numbers, leading to robust immunoresponses and efficient production of the anti-antigen antibodies and CD8+ T cells. Thus, the aluminum-based nanocarriers, especially the PEG-PLANs, are a promising VADS possessing the potential of eliciting strong and comprehensive immunity against pathogens.