Rabies is a zoonotic disease that still causes 59,000 human deaths each year,and rabies vaccine is the most effective way to control the disease.Our previous studies suggested that the maturation of DC plays an import...Rabies is a zoonotic disease that still causes 59,000 human deaths each year,and rabies vaccine is the most effective way to control the disease.Our previous studies suggested that the maturation of DC plays an important role in enhancing the immunogenicity of rabies vaccine.Flt3L has been reported to own the ability to accelerate the DC maturation,therefore,in this study,a recombinant rabies virus expressing mouse Flt3L,designated as LBNSE-Flt3L,was constructed,and its immunogenicity was characterized.It was found that LBNSE-FU3L could enhance the maturation of DC both in vitro and in vivo,and significantly more TFH cells and Germinal Center B(GC B)cells were generated in mice immunized with LBNSE-FU3L than those immunized with the parent virus LBNSE.Consequently,expressing of Flt3L could elevate the level of virus-neutralizing antibodies(VNA)in immunized mice which provides a better protection from a lethal rabies virus challenge.Taken together,our study extends the potential of Flt3L as a good adjuvant to develop novel rabies vaccine by enhancing the VNA production through activating the DC—Tfh^GC B axis in immunized mice.展开更多
基金supported by the National Program on Key Research Project of China (2016YFD0500400 and 2017YFD0501701)the National Natural Science Foundation of China (31872494, 31402176, 31372419, and 31522057)+2 种基金the Fundamental Research Funds for the Central Universities (No. 2662016QD036 to MZ)the Ministry of Science and Technology of China (863 program, No. 2011AA10A212)the Ministry of Agriculture of China (Special Fund for Agro-scientific Research in the Public Interest, No. 201303042 to ZFF)
文摘Rabies is a zoonotic disease that still causes 59,000 human deaths each year,and rabies vaccine is the most effective way to control the disease.Our previous studies suggested that the maturation of DC plays an important role in enhancing the immunogenicity of rabies vaccine.Flt3L has been reported to own the ability to accelerate the DC maturation,therefore,in this study,a recombinant rabies virus expressing mouse Flt3L,designated as LBNSE-Flt3L,was constructed,and its immunogenicity was characterized.It was found that LBNSE-FU3L could enhance the maturation of DC both in vitro and in vivo,and significantly more TFH cells and Germinal Center B(GC B)cells were generated in mice immunized with LBNSE-FU3L than those immunized with the parent virus LBNSE.Consequently,expressing of Flt3L could elevate the level of virus-neutralizing antibodies(VNA)in immunized mice which provides a better protection from a lethal rabies virus challenge.Taken together,our study extends the potential of Flt3L as a good adjuvant to develop novel rabies vaccine by enhancing the VNA production through activating the DC—Tfh^GC B axis in immunized mice.
