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Mucosal vaccines have great potential and advantages in preventing infection caused by multiple pathogens. In developing mucosal vaccines, the biggest challenge comes from finding safe and effective adjuvants and drug delivery systems. Great progress has been made in the generation of mucosal adjuvants using detoxified bacterial toxin derivatives, pathogen-related molecules, cytokines, and various vaccine delivery systems. However, many problems, relating to the safety and efficacy of mucosal vaccine adjuvants, remain. Certain natural substances can boost the immune response and thus could be used as adjuvants in vaccination. These natural-product-based immune adjuvants have certain advantages over conventional adjuvants, such as low toxicity, high stability, and low cost of production. In this review, we summarize the latest natural-product-based immune adjuvants, and discuss their properties and clinical applications.

ObjectivesHuman leucocyte antigen B27 (HLA-B27) is an important biomarker for ankylosing spondylitis (AS). However, delay in the diagnosis of AS is still common in clinical practice. Several single nucleotide polymorphisms (SNPs) in the coding gene of tumor necrosis factor alpha (TNFα) have been reported to be AS susceptibility loci. Our aim was to explore whether SNPs in TNFα could be used to improve the performance of HLA-B27 for predicting AS.MethodsFive SNPs (rs1799964, rs1800630, rs1799724, rs1800629, and rs361525) spanning TNFα were genotyped by qPCR-Invader assay in 93 AS patients and 107 healthy controls for association analysis and linkage disequilibrium (LD) analysis. Random forest algorithm was utilized to construct the predictive classifiers for AS. HLA-B was genotyped by PCR-sequence-based typing in a subset of the HLA-B27-positive subjects (38 AS patients and 5 healthy controls).ResultsThe T allele of rs1799724 was verified to significantly increase the risk of AS (OR = 4.583, p < 0.0001), while the A allele of rs361525 showed an association with the reduced AS risk (OR = 0.168, p = 0.009). In addition, the rs1799964T-rs1800630C-rs1799724T-rs1800629G-rs361525G haplotype was significantly associated with a higher risk of AS (p < 0.0001). The optimal set of variables for classifiers to predict AS only consisted of HLA-B27. Strong associations with HLA-B27 status were found in both rs1799724 (p < 0.0001) and rs361525 (p = 0.001), and all the analyzed HLA-B27-positive subjects carried HLA-B*27:04 or HLA-B*27:05.ConclusionIn the Chinese Han population, the minor allele T of rs1799724 could increase the risk of AS, while the minor allele A of rs361525 protects individuals from AS. However, the contributions of rs1799724 and rs361525 to AS risk were dependent on HLA-B27 status, suggesting the importance of taking the independence and specificity into consideration in AS susceptibility loci studies.