Specific T cell induction using iron oxide based nanoparticles as subunit vaccine adjuvant

Abstract

Metal-based nanoparticles (NPs) stimulate innate immunity; however, they have never been demonstrated to be capable of aiding the generation of specific cellular immune responses. Therefore, our objective was to evaluate whether iron oxide-based NPs have adjuvant properties in generating cellular Th1, Th17 and TCD8 (Tc1) immune responses. For this purpose, a fusion protein (CMX) composed of Mycobacterium tuberculosis antigens was used as a subunit vaccine. Citrate-coated MnFeO NPs were synthesized by co-precipitation and evaluated by transmission electron microscopy. The vaccine was formulated by homogenizing NPs with the recombinant protein, and protein corona formation was determined by dynamic light scattering and field-emission scanning electron microscopy. The vaccine was evaluated for the best immunization route and strategy using subcutaneous and intranasal routes with 21-day intervals between immunizations. When administered subcutaneously, the vaccine generated specific CD4IFN-γ (Th1) and CD8IFN-γ responses. Intranasal vaccination induced specific Th1, Th17 (CD4IL-17) and Tc1 responses, mainly in the lungs. Finally, a mixed vaccination strategy (2 subcutaneous injections followed by one intranasal vaccination) induced a Th1 (in the spleen and lungs) and splenic Tc1 response but was not capable of inducing a Th17 response in the lungs. This study shows for the first time a subunit vaccine with iron oxide based NPs as an adjuvant that generated cellular immune responses (Th1, Th17 and TCD8), thereby exhibiting good adjuvant qualities. Additionally, the immune response generated by the subcutaneous administration of the vaccine diminished the bacterial load of Mtb challenged animals, showing the potential for further improvement as a vaccine against tuberculosis.

Biodistribution and toxicity of epitope‐functionalized dextran iron oxide nanoparticles in a pregnant murine model

“…Previously, we demonstrated SNAREs co‐incubated with DCs or macrophages for 24 and 48 hr did not induce maturation (Bolandparvaz et al, ). This finding is seminal to our SNARE formulation to evade an immune response and prevent generation of antibodies, as reported with adjuvant‐coated NPs (Neto, de Sousa‐Júnior, da Costa, & Kipnis, ). Here, we examined the production of IL‐10 and IL‐12 as these are the primary cytokines produced by activated APCs (Ma, Yan, Zheng, et al, ).…”

Metal nanomaterials: Immune effects and implications of physicochemical properties on sensitization, elicitation, and exacerbation of allergic disease

“…Contrarily, when FeNP and OVA were co-administered intravenously or subcutaneously, enhanced antibody responses were seen in mice (Powles et al 2017; Shen I et al 2018). Similar immune-stimulating effects of FeNP have been demonstrated when used as an adjuvant by various exposure routes during immunization to various other antigens in the context of vaccine studies (Pusic et al 2013; Hoang et al 2015; Sungsuwan et al 2015; Neto et al 2018; Zhao et al 2018).…”

Metal Oxide Nanoparticles as Biomedical Materials

“…MONPs are also used to enhance the protective and long-lasting immune response of the safer but less immunogenic subunit vaccine than live attenuated vaccines. Citrate-coated MnFe 2 O 4 NPs with protein corona of the fusion protein (CMX) composed of Mycobacterium tuberculosis antigens were proved to be capable of aiding the generation of the specific cellular immune response (T-helper 1, T-helper 17 and TCD8) [101]. Besides bacteria antigens, Fe 2 O 3 NPs have been utilized in the creation of virus-like particles (VLP) that proved their exceptional use as vaccines, gene-carrying nanocontainers, MRI contrast agents and drug delivery vectors [102].…”