The Adjuvanticity And Application Of Trichosanthin

BACKGROUND AND PURPOSE: Influenza causes regional or worldwide pandemic with high morbidity and mortality.Although vaccination is considered as one of the most important preventive strategies against influenza,slow production process and the supply shortage of trivalent inactivated vaccine during a pandemic are currently significant limitations.It has been demonstrated that introduction of adjuvant into vaccine can enhance the immunogenicity and thus indirectly increase the production of vaccine via lowering the antigen dose.So far,no adjuvant has been used with the influenza vaccine in China.The primary concern is on the safety and side effects of the current adjuvant.In this study,we explored the feasibility of using trichosanthin as a novel adjuvant of vaccine in a mouse model,and specifically investigated the adjuvanticity of trichosanthin in developing new type of adjuvanted vaccine with effective immunogenicity and strong immunological protection against influenza virus.METHODS: In mice immunized intramuscularly with trichosanthin mixed with ovalbumin(OVA)and commercialized unadjuvanted trivalent inactivated influenza vaccine(Fluarix),specific humoral and cellular immune responses were analyzed to explore the potential of trichosanthin as a new adjuvant candidate derived from a Chinese herbal medicine.The immunogenicity and protective efficacy of the mixture of trichosanthin and Fluarix were subsequently evaluated through challenge assay.RESULTS: In mice immunized with OVA and trichosanthin,inclusion of trichosanthin induced higher levels of OVA specific IgG and IgG subtype antibodies and enhanced in vitro cytokines secretion,in comparison to OVA alone.Low dose of trichosanthin,as an adjuvant candidate for seasonal influenza vaccine,induced higher level of antigen specific antibody titer,and leaded to more effective hemagglutination inhibition and neutralizing activity,which provided the mouse with a better protection against homologous and homologous drift influenza virus at high lethal dose.CONCLUSIONS: Trichosanthin could be used as an effective adjuvant in the vaccine development.Combination of trichosanthin with seasonal influenza vaccine was found to accelerate the antibody response,to enhance the immunogenicity of vaccine,and to improve both humoral and cellular immunity,which eventually conferred increased protection from influenza infection in a mouse model.This study provides a basis to develop an effective strategy for solving the limited capacity of current influenza vaccine.