Hepatitis A virus(HAV)live-attenuated vaccine H2 strain has been approved for clinical use for decades with ideal safety profiles in nonhuman primate models and humans.Recently,type Ⅰ interferon(IFN)receptor-deficien...Hepatitis A virus(HAV)live-attenuated vaccine H2 strain has been approved for clinical use for decades with ideal safety profiles in nonhuman primate models and humans.Recently,type Ⅰ interferon(IFN)receptor-deficient mice were shown to be susceptible to HAV infection.Herein,we sought to determine the infection and replication dynamics of the H2 in Ifnar^(-/-)mice that lack type Ⅰ IFN receptor.Following intravenous injection,the H2 failed to cause obvious clinical symptoms in Ifnar^(-/-)mice,and no significant upregulation in serum alanine aminotransferase(ALT)levels was observed.Notably,the histopathological examination showed that there were significant focal infiltrations of lymphocytes and neutrophils in the portal area,but no focal necrosis was observed in liver tissues.Viral RNAs sustained in the liver,and the infectious virus could be recovered from the liver tissue until 42 days post-infection.More importantly,H2 infection induced obvious viremia and persistent viral shedding in feces.In addition,robust HAV-specific humoral immune responses were induced in Ifnar^(-/-)mice.Overall,our study revealed the safety profile of H2 in Ifnar^(-/-)mice,which not only helps understand the attenuation mechanism of H2,but also expands the application of the Ifnar^(-/-)mouse model for HAV studies.展开更多
Pseudorabies virus(PRV)is a double-stranded DNA virus with a genome approximating 150 kb in size.PRV contains many non-essential genes that can be replaced with genes encoding heterogenous antigens without affecting v...Pseudorabies virus(PRV)is a double-stranded DNA virus with a genome approximating 150 kb in size.PRV contains many non-essential genes that can be replaced with genes encoding heterogenous antigens without affecting viral propagation.With the ability to induce cellular,humoral and mucosal immune responses in the host,PRV is considered to be an ideal and potential live vector for generation of animal vaccines.In this review,we summarize the advances in attenuated recombinant PRVs and design of PRV-based live vaccines as well as the challenge of vaccine application.展开更多
Infectious bronchitis(IB) is a highly contagious avian disease caused by infection with infectious bronchitis virus(IBV),which seriously affects the development of the global poultry industry. The distribution of TW I...Infectious bronchitis(IB) is a highly contagious avian disease caused by infection with infectious bronchitis virus(IBV),which seriously affects the development of the global poultry industry. The distribution of TW I-type IBV in China has increased in recent years, becoming a widespread genotype. We previously isolated a TW I-type IBV strain termed CK/CH/GD/GZ14 in 2014, but its pathogenicity and possibility for vaccine development were not explored. Therefore, this research aimed to develop a live-attenuated virus vaccine based on the CK/CH/GD/GZ14 strain. The wild type IBV CK/CH/GD/GZ14 strain was serially passaged in SPF embryos for 145 generations. The morbidity and mortality rate of wildtype strain in 14 day-old chickens is 100% and 80% respectively, while the morbidity rate in the attenuated strain was 20%in the 95 th and 105 th generations and there was no death. Histopathological observations showed that the pathogenicity of the 95th and 105th generations in chickens was significantly weakened. Further challenge experiments confirmed that the attenuated CK/CH/GD/GZ14 strain in the 95th and 105 th generations could resist CK/CH/GD/GZ14(5th generation)infection and the protection rate was 80%. Tracheal cilia stagnation, virus shedding, and viral load experiments confirmed that the 95 th and 105th generations provide good immune protection in chickens, and the immunogenicity of the 105th generation is better than that of the 95th generation. These data suggest that the attenuated CK/CH/GD/GZ14 strain in the105th generation may be applied as a vaccine candidate against TW I-type IBV.展开更多
In nature,a limited,conservative set of amino acids are utilized to synthesize proteins.Genetic code expansion technique reassigns codons and incorporates noncanonical amino acids(ncAAs)through orthogonal aminoacyltRN...In nature,a limited,conservative set of amino acids are utilized to synthesize proteins.Genetic code expansion technique reassigns codons and incorporates noncanonical amino acids(ncAAs)through orthogonal aminoacyltRNA synthetase(aaRS)/tRNA pairs.The past decade has witnessed the rapid growth in diversity and scope for therapeutic applications of this technology.Here,we provided an update on the recent progress using genetic code expansion in the following areas:antibody-drug conjugates(ADCs),bispecific antibodies(BsAb),immunotherapies,long-lasting protein therapeutics,biosynthesized peptides,engineered viruses and cells,as well as other therapeutic related applications,where the technique was used to elucidate the mechanisms of biotherapeutics and drug targets.展开更多
基金supported by the National Natural Science Fund for Distinguished Young Scholar (No.81925025)the Innovative Research Group (No. 81621005) from the National Natural Science Foundation of Chinathe Innovation Fund for Medical Sciences (No. 2019-I2M-5-049) from the Chinese Academy of Medical Sciences
文摘Hepatitis A virus(HAV)live-attenuated vaccine H2 strain has been approved for clinical use for decades with ideal safety profiles in nonhuman primate models and humans.Recently,type Ⅰ interferon(IFN)receptor-deficient mice were shown to be susceptible to HAV infection.Herein,we sought to determine the infection and replication dynamics of the H2 in Ifnar^(-/-)mice that lack type Ⅰ IFN receptor.Following intravenous injection,the H2 failed to cause obvious clinical symptoms in Ifnar^(-/-)mice,and no significant upregulation in serum alanine aminotransferase(ALT)levels was observed.Notably,the histopathological examination showed that there were significant focal infiltrations of lymphocytes and neutrophils in the portal area,but no focal necrosis was observed in liver tissues.Viral RNAs sustained in the liver,and the infectious virus could be recovered from the liver tissue until 42 days post-infection.More importantly,H2 infection induced obvious viremia and persistent viral shedding in feces.In addition,robust HAV-specific humoral immune responses were induced in Ifnar^(-/-)mice.Overall,our study revealed the safety profile of H2 in Ifnar^(-/-)mice,which not only helps understand the attenuation mechanism of H2,but also expands the application of the Ifnar^(-/-)mouse model for HAV studies.
基金supported by the Natural Science Foundation of China(grants 32072869,31941015)Shandong Modern Technology System of Agricultural Industry(SDAIT-09-06).
文摘Pseudorabies virus(PRV)is a double-stranded DNA virus with a genome approximating 150 kb in size.PRV contains many non-essential genes that can be replaced with genes encoding heterogenous antigens without affecting viral propagation.With the ability to induce cellular,humoral and mucosal immune responses in the host,PRV is considered to be an ideal and potential live vector for generation of animal vaccines.In this review,we summarize the advances in attenuated recombinant PRVs and design of PRV-based live vaccines as well as the challenge of vaccine application.
基金This study was supported by the Key Research and Development Program of Guangdong Province(2020B020222001)the Construction of Modern Agricultural Science and Technology Innovation Alliance in Guangdong Province(2020KJ128)+5 种基金the Natural Science Foundation of Guangdong Province(2019A1515012006)the National Natural Science Foundation of China(31902252)the Special Project of National Modern Agricultural Industrial Technology System(CARS-41)the National Modern Agricultural Industry Science and Technology Innovation Center in Guangzhou(2018kczx01)the National Key R&D Program of China(2017YFD0502001)the Creation of a Triple Chimeric Vaccine(rIBV-ND-H9)Using Avian Infectious Bronchitis Attenuated D90 as a Vector(2017KZDM008)。
文摘Infectious bronchitis(IB) is a highly contagious avian disease caused by infection with infectious bronchitis virus(IBV),which seriously affects the development of the global poultry industry. The distribution of TW I-type IBV in China has increased in recent years, becoming a widespread genotype. We previously isolated a TW I-type IBV strain termed CK/CH/GD/GZ14 in 2014, but its pathogenicity and possibility for vaccine development were not explored. Therefore, this research aimed to develop a live-attenuated virus vaccine based on the CK/CH/GD/GZ14 strain. The wild type IBV CK/CH/GD/GZ14 strain was serially passaged in SPF embryos for 145 generations. The morbidity and mortality rate of wildtype strain in 14 day-old chickens is 100% and 80% respectively, while the morbidity rate in the attenuated strain was 20%in the 95 th and 105 th generations and there was no death. Histopathological observations showed that the pathogenicity of the 95th and 105th generations in chickens was significantly weakened. Further challenge experiments confirmed that the attenuated CK/CH/GD/GZ14 strain in the 95th and 105 th generations could resist CK/CH/GD/GZ14(5th generation)infection and the protection rate was 80%. Tracheal cilia stagnation, virus shedding, and viral load experiments confirmed that the 95 th and 105th generations provide good immune protection in chickens, and the immunogenicity of the 105th generation is better than that of the 95th generation. These data suggest that the attenuated CK/CH/GD/GZ14 strain in the105th generation may be applied as a vaccine candidate against TW I-type IBV.
基金We thank the following agencies for financial support on related ongoing projects in our lab:National Key Research and Development Program of China(No.2016YFA0201400)the National Natural Science Foundation of China(21778005)+1 种基金Peking University Health Science Center(BMU20160537 and BMU2017QQ006)Youth Thousand-Talents Program of China。
文摘In nature,a limited,conservative set of amino acids are utilized to synthesize proteins.Genetic code expansion technique reassigns codons and incorporates noncanonical amino acids(ncAAs)through orthogonal aminoacyltRNA synthetase(aaRS)/tRNA pairs.The past decade has witnessed the rapid growth in diversity and scope for therapeutic applications of this technology.Here,we provided an update on the recent progress using genetic code expansion in the following areas:antibody-drug conjugates(ADCs),bispecific antibodies(BsAb),immunotherapies,long-lasting protein therapeutics,biosynthesized peptides,engineered viruses and cells,as well as other therapeutic related applications,where the technique was used to elucidate the mechanisms of biotherapeutics and drug targets.
