We demonstrated that administration in an intranasal vaccination system raised DT-specific mucosal and serum

The restored KLF4 expression inhibited the cervical cancer cell survival in the treatment of cisplatin. We conclude that the promoter hypermethylation of KLF4 inactivates its function as a tumor suppressor in cervical carcinogenesis. Mucosal immunization has several distinct advantages over injection, including the stimulation of systemic immunity and mucosal immunity at the application site and other mucosa, including the lung and gastrointestinal tract mucosa. However, the immunogenicity of synthetic proteins or peptide antigens is generally weak, whereas non-living vaccines administered at mucosal sites are possibly ineffective and can even lead to mucosal tolerance. Therefore, an adjuvant that potentiates the induction of appropriate immune responses to such antigens in the mucosa, as well as the organs, is required for the development of mucosal vaccines. CpG oligodeoxynucleotides, the synthetic counterparts of bacterial DNA, are currently tested in clinical trials as adjuvants for multiple immunotherapies, and these compounds have shown safety profiles similar to conventional vaccines. The A class stimulates IFN-a production in plasmacytoid dendritic cells, whereas the B class strongly activates B cells. Both activities are elicited upon binding to Toll-like receptor 9. The activation of pDCs and IFN-a production are important parameters in the assessment of influenza vaccine immunogenicity. Certain vaccines, such as MMR and rabies vaccines, stimulate IFN-a production from pDCs in a manner similar to A class CpG ODNs. On the other hand, the effects of CpG ODNs, primarily B class with a phosphorothioate backbone, were reported to differ with the administration route, schedule and sequence. In some cases, they may even cause lymphoid follicle destruction or immunosuppression in a pDC-independent manner. In this regard, CpG ODNs with a phosphodiester backbone similar to bacterial DNA TWS119 instead of PS, and capable of inducing IFN-a production, could be advantageous as adjuvants. They could induce TH1 immunity through activation of pDCs, and then processed inside the target cells. In the present study, we investigated the adjuvanticity of G9.1 in an intranasal vaccination system using diphtheria toxoid as an antigen. DT mainly induces humoral immunity, but also TH2-mediated immunity when used with the well-known adjuvant cholera toxin. This combination allows further evaluation of TH1 immunity induction by G9.1. Protective immunity can be evaluated without the challenge experiment because international standards regarding antitoxin titer reflecting protection from diphtheria have been established. Furthermore, DT is appropriate as an antigen for the investigation of mucosal immunity because Corynebacterium diphtheriae primarily infects the mucosal surface in the pharynx, larynx and nose.

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