Cholesterol-25-hydroxylase(CH25 H)and its enzymatic product 25-hydroxy cholesterol(25 HC)exert broadly antiviral activity including inhibiting HIV-1 infection.However,their antiviral immunity and therapeutic efficacy ...Cholesterol-25-hydroxylase(CH25 H)and its enzymatic product 25-hydroxy cholesterol(25 HC)exert broadly antiviral activity including inhibiting HIV-1 infection.However,their antiviral immunity and therapeutic efficacy in a nonhuman primate model are unknown.Here,we report that the regimen of 25 HC combined with antiretroviral therapy(ART),provides profound immunological modulation towards inhibiting viral replication in chronically SIVmac239-infected rhesus macaques(RMs).Compared to the ART alone,this regimen more effectively controlled SIV replication,enhanced SIVspecific cellular immune responses,restored the ratio of CD4/CD8 cells,reversed the hyperactivation state of CD4^(+)T cells,and inhibited the secretion of proinflammatory cytokines by CD4^(^(+))and CD8^(+)T lymphocytes in chronically SIVinfected RMs.Furthermore,the in vivo safety and the preliminary pharmacokinetics of the 25 HC compound were assessed in this RM model.Taken together,these assessments help explain the profound relationship between cholesterol metabolism,immune modulation,and antiviral activities by 25 HC.These results provide insight for developing novel therapeutic drug candidates against HIV-1 infection and other related diseases.展开更多
Background Various modalities of vaccines against coronavirus disease 2019(COVID-19),based on different platforms and immunization procedures,have been successively approved for marketing worldwide.A comprehensive rev...Background Various modalities of vaccines against coronavirus disease 2019(COVID-19),based on different platforms and immunization procedures,have been successively approved for marketing worldwide.A comprehensive review for clinical trials assessing the safety of COVID-19 vaccines is urgently needed to make an accurate judgment for mass vaccination.Main text A systematic review and meta-analysis was conducted to determine the safety of COVID-19 vaccine candidates in randomized controlled trials(RCTs).Data search was performed in PubMed,Embase,Cochrane library,Scopus,Web of Science,and MedRxiv.Included articles were limited to RCTs on COVID-19 vaccines.A total of 73,633 subjects from 14 articles were included to compare the risks of adverse events following immunization(AEFI)after vaccinating different COVID-19 vaccines.Pooled risk ratios(RR)of total AEFI for inactivated vaccine,viral-vectored vaccine,and mRNA vaccine were 1.34[95%confidence interval(CI)1.11–1.61,P<0.001],1.65(95%CI 1.31–2.07,P<0.001),and 2.01(95%CI 1.78–2.26,P<0.001),respectively.No significant differences on local and systemic AEFI were found between the first dose and second dose.In addition,people aged≤55 years were at significantly higher risk of AEFI than people aged≥56 years,with a pooled RR of 1.25(95%CI 1.15–1.35,P<0.001).Conclusions The safety and tolerance of current COVID-19 vaccine candidates are acceptable for mass vaccination,with inactivated COVID-19 vaccines candidates having the lowest reported AEFI.Long-term surveillance of vaccine safety is required,especially among elderly people with underlying medical conditions.展开更多
基金supported by the National Natural Science Foundation of China(81971927,31870912,32000124)the National Science and Technology Major Project of China(2018ZX10731101-002)+4 种基金the National Key Research and Development Program of China(2018YFA0900803)the Science and Technology Planning Project of Shenzhen City(20190804095916056,JCYJ20200109142601702)the High Level Project of Medicine in Longhua,Shenzhen(HLPM201907020105)China Postdoctoral Science Foundation(Grant No.2019M663140)the Municipal Health and Medical cooperation innovation Major Project of Guangzhou City(201704020219,201803040002)。
文摘Cholesterol-25-hydroxylase(CH25 H)and its enzymatic product 25-hydroxy cholesterol(25 HC)exert broadly antiviral activity including inhibiting HIV-1 infection.However,their antiviral immunity and therapeutic efficacy in a nonhuman primate model are unknown.Here,we report that the regimen of 25 HC combined with antiretroviral therapy(ART),provides profound immunological modulation towards inhibiting viral replication in chronically SIVmac239-infected rhesus macaques(RMs).Compared to the ART alone,this regimen more effectively controlled SIV replication,enhanced SIVspecific cellular immune responses,restored the ratio of CD4/CD8 cells,reversed the hyperactivation state of CD4^(+)T cells,and inhibited the secretion of proinflammatory cytokines by CD4^(^(+))and CD8^(+)T lymphocytes in chronically SIVinfected RMs.Furthermore,the in vivo safety and the preliminary pharmacokinetics of the 25 HC compound were assessed in this RM model.Taken together,these assessments help explain the profound relationship between cholesterol metabolism,immune modulation,and antiviral activities by 25 HC.These results provide insight for developing novel therapeutic drug candidates against HIV-1 infection and other related diseases.
文摘Background Various modalities of vaccines against coronavirus disease 2019(COVID-19),based on different platforms and immunization procedures,have been successively approved for marketing worldwide.A comprehensive review for clinical trials assessing the safety of COVID-19 vaccines is urgently needed to make an accurate judgment for mass vaccination.Main text A systematic review and meta-analysis was conducted to determine the safety of COVID-19 vaccine candidates in randomized controlled trials(RCTs).Data search was performed in PubMed,Embase,Cochrane library,Scopus,Web of Science,and MedRxiv.Included articles were limited to RCTs on COVID-19 vaccines.A total of 73,633 subjects from 14 articles were included to compare the risks of adverse events following immunization(AEFI)after vaccinating different COVID-19 vaccines.Pooled risk ratios(RR)of total AEFI for inactivated vaccine,viral-vectored vaccine,and mRNA vaccine were 1.34[95%confidence interval(CI)1.11–1.61,P<0.001],1.65(95%CI 1.31–2.07,P<0.001),and 2.01(95%CI 1.78–2.26,P<0.001),respectively.No significant differences on local and systemic AEFI were found between the first dose and second dose.In addition,people aged≤55 years were at significantly higher risk of AEFI than people aged≥56 years,with a pooled RR of 1.25(95%CI 1.15–1.35,P<0.001).Conclusions The safety and tolerance of current COVID-19 vaccine candidates are acceptable for mass vaccination,with inactivated COVID-19 vaccines candidates having the lowest reported AEFI.Long-term surveillance of vaccine safety is required,especially among elderly people with underlying medical conditions.
