Biodegradable Imiquimod-Loaded Mesoporous Organosilica as a Nanocarrier and Adjuvant for Enhanced and Prolonged Immunity against Foot-and-Mouth Disease Virus in Mice

Abstract

Foot-and-mouth disease (FMD), a serious, fast-spreading, and virulent disease, has led to huge economic losses to people all over the world. Vaccines are the most effective way to control FMD. However, the weak immunogenicity of inactivated FMD virus (FMDV) requires the addition of adjuvants to enhance the immune effectiveness of the vaccines. Herein, we formulated and fabricated biodegradable dendritic mesoporous tetrasulfide-doped organosilica nanoparticles SOMSN with imiquimod complex (SOMSN-IMQ) and used it as a platform for FMD vaccine delivery and as an adjuvant. SOMSN-IMQ demonstrated excellent stability for 6 months when stored in PBS, while it could be completely degraded within 42 days in SBF at room temperature. Biosafety experiments such as cell toxicity, hemolysis, and histology indicated that the as-prepared SOMSN-IMQ showed nontoxicity and good biocompatibility. Furthermore, SOMSN-IMQ exhibited a maximum adsorption capacity of 1000 μg/mg for inactivated FMDV antigens. Our results showed that SOMSN-IMQ can be effectively engulfed by RAW264.7 cells in a dose-dependent manner. After immunization, SOMSN-IMQ@FMDV can elicit persistent higher antibody levels, higher IgG2a/IgG1 ratio, and cytokine expression, which indicated that SOMSN-IMQ@FMDV triggered superior humoral and cellular immune responses. Moreover, SOMSN-IMQ could provoke maturation and activation of dendritic cells in lymph nodes (LDCs) as well as the proliferation of lymphocytes in vivo. Thus, SOMSN-IMQ could promote effective and potent immunity and provide a promising adjuvant platform for FMDV vaccination with acceptable safety.

Synthesis of a crystalline zeolitic imidazole framework-8 nano-coating on single environment-sensitive viral particles for enhanced immune responses

“…60,62,63 The absolute value of the CD4 + T cell in our work was relatively lower than the results of other literature, which varies from 10% to 40%. [60][61][62][63][64][65][66] However, compared with naked 146S, both CD4 + T and CD 8 + T cells by using 146S@ZIF-8 were statistically higher (Fig. 6c and d).…”

Alginate di-aldehyde-modified metal–organic framework nanocarriers as delivery platform and adjuvant in inactivated pseudorabies vaccination

“…The cytotoxicity of ZIF-7/8 and ZIF-7/8-ADA NPs on RAW264.7 cells was detected using an CCK-8 assay kit. 41,42 RAW264.7 cells were seeded in 96-well plates in high-glucose Dulbecco's modified Eagle's medium (DMEM), supplemented with 10% FBS with 5% CO 2 at 37 1C and incubated overnight for the cells to adhere. 100 mL of each sample with different concentrations in the range of 0-1000 mg mL À1 was added to the cells.…”

Adjuvant physiochemistry and advanced nanotechnology for vaccine development

“…Some nanotechnology adjuvants were deployed in the development of vaccines against other diseases, such as MnFe 2 O 4 nanoparticle adjuvanted vaccine against tuberculosis, 538 Ca 3 (PO) 4 , Al(OH) 3 or chitosan nanoparticle adjuvanted vaccine against brucellosis, 539 and MSN adjuvanted vaccine against foot-and-mouth disease. 540 The exemplified nanotechnology adjuvanted vaccines against infectious diseases are summarized in Table 5.…”