Inhibitory effects of TLR7/8 ligand R-848 on IgE production of murine in vivo

Objective To investigate whether R-848 could inhibit IgE production of mice immunized with OVA plus ALUM in vivo.Methods BALB/c mice were immunized s.c on the back with PBS,OVA,OVA plus R-848,OVA plus CpG,OVA plus ALUM,and OVA plus ALUM in R-848 or CpG every two weeks for three times.The blood from the mice was harvested after the last immunization,and the concentration of OVA specific or total IgE,IgG1 and IgG2a in the sera was determined;the splenocytes from the immunized mice were harvested and cultured with or without OVA for 3 days,and the concentration of IL-4 and IFNγ in the supernatants was determined.Results Firstly,we investigated that R-848 as Th1 adjuvant could enhance the production of OVA specific IgG2a in mice immunized with OVA.Secondly,further study showed that R-848 could inhibit the production of OVA specific IgE and total IgE,and promote the production of OVA specific IgG2a in the sera of mice immunized with OVA plus ALUM.Moreover,the results of ELISA showed that R-848 inhibiting IgE production was related to its reducing IL-4 production and enhancing IFNγ production.Conclusion R-848 could inhibit IgE production of mice immunized with OVA plus ALUM in vivo.

PIKA as an Adjuvant Enhances Specific Humoral and Cellular Immune Responses Following the Vaccination of Mice with HBsAg plus PIKA

An adjuvant is usually used to enhance the immune response induced by vaccines. The choice of adjuvant or immune enhancer determines the effectiveness of the immune response. Currently, aluminium （Alum, a generic term for salts of aluminium） is the only FDA-approved adjuvant. Alum predominantly induces the differentiation of Th2 cells and thus mediates an antibody immune response. Therefore, there is an urgent need for new adjuvants that enhance not only humoral but also cellular immune responses. In the present study, we demonstrates that PIKA （a stabilized dsRNA） as an adjuvant directly induces the activation and the proliferation of both B and NK cells in vitro. Injection of PIKA into mice results in the production of cytokines in vivo. In addition, the study demonstrates that PIKA promotes the maturation of bone marrow-derived dendritic cells （BMDCs） including up-regulation of the co-stimulatory molecules CD80, CD86 and CD40, and the induction of cytokines such as IL-12p70, IL-12p40 and IL-6. Importantly, after immunization of mice with HBsAg plus PIKA, the presence of PIKA enhances the titers of HBsAg-specific IgG and HBsAg-specific IFN-γ production. These results demonstrate that PIKA as an adjuvant can promote both humoral and cellular immune responses. These might have an implication in applying PIKA as an adjuvant to be used in the design and development of both therapeutic and preventive vaccines, and used in the clinical study.