Natural killer T(NKT)cells activated with the glycolipid ligandα-galactosylceramide(α-GalCer)stimulate a wide variety of immune cells that enhance vaccine-mediated immune responses.Several studies have used this app...Natural killer T(NKT)cells activated with the glycolipid ligandα-galactosylceramide(α-GalCer)stimulate a wide variety of immune cells that enhance vaccine-mediated immune responses.Several studies have used this approach to adjuvant inactivated and subunit infuenza A virus(IAV)vaccines,including to enhance cross-protective infuenza immunity.However,less is known about whetherα-GalCer can enhance live attenuated infuenza virus(LAIV)vaccines,which usually induce superior heterologous and heterosubtypic immunity compared to non-replicating infuenza vaccines.The current study used the swine infuenza challenge model to assess whetherα-GalCer can enhance cross-protective immune responses elicited by a recombinant H3N2 LAIV vaccine(TX98ΔNS1)encoding a truncated NS1 protein.In one study,weaning pigs were administered the H3N2 TX98ΔNS1 LAIV vaccine with 0,10,50,and 100μg/kg doses ofα-GalCer,and subsequently challenged with a heterologous H3N2 virus.All treatment groups were protected from infection.However,the addition ofα-GalCer appeared to suppress nasal shedding of the LAIV vaccine.In another experiment,pigs vaccinated with the H3N2 LAIV,with or without 50μg/kg ofα-GalCer,were challenged with the heterosubtypic pandemic H1N1 virus.Pigs vaccinated with the LAIV alone generated cross-reactive humoral and cellular responses which blocked virus replication in the airways,and signifcantly decreased virus shedding.On the other hand,combining the vaccine withα-GalCer reduced cross-protective cellular and antibody responses,and resulted in higher virus titers in respiratory tissues.These fndings suggest that:(i)high doses ofα-GalCer impair the replication and nasal shedding of the LAIV vaccine;and(ii)α-GalCer might interfere with heterosubtypic cross-protective immune responses.This research raise concerns that should be considered before trying to use NKT cell agonists as a possible adjuvant approach for LAIV vaccines.展开更多
Background:School closure is a common mitigation strategy during severe infuenza epidemics and pandemics.However,the efectiveness of this strategy remains controversial.In this study,we aimed to explore the efectivene...Background:School closure is a common mitigation strategy during severe infuenza epidemics and pandemics.However,the efectiveness of this strategy remains controversial.In this study,we aimed to explore the efectiveness of school closure on seasonal infuenza epidemics in provincial-level administrative divisions(PLADs)with varying urbanization rates in China.Methods:This study analyzed infuenza surveillance data between 2010 and 2019 provided by the Chinese National Infuenza Center.Taking into consideration the climate,this study included a region with 3 adjacent PLADs in Northern China and another region with 4 adjacent PLADs in Southern China.The efect of school closure on infuenza transmission was evaluated by the reduction of the efective reproductive number of seasonal infuenza during school winter breaks compared with that before school winter breaks.An age-structured Susceptible-Infected-Recovered-Susceptible(SIRS)model was built to model infuenza transmission in diferent levels of urbanization.Parameters were determined using the surveillance data via robust Bayesian method.Results:Between 2010 and 2019,in the less urbanized provinces:Hebei,Zhejiang,Jiangsu and Anhui,during school winter breaks,the efective reproductive number of seasonal infuenza epidemics reduced 14.6%[95%confdential interval(CI):6.2–22.9%],9.6%(95%CI:2.5–16.6%),7.3%(95%CI:0.1–14.4%)and 8.2%(95%CI:1.1–15.3%)respectively.However,in the highly urbanized cities:Beijing,Tianjin and Shanghai,it reduced only 5.2%(95%CI:-0.7–11.2%),4.1%(95%CI:-0.9–9.1%)and 3.9%(95%CI:-1.6–9.4%)respectively.In China,urbanization is associated with decreased proportion of children and increased social contact.According to the SIRS model,both factors could reduce the impact of school closure on seasonal infuenza epidemics,and the proportion of children in the population is thought to be the dominant infuencing factor.Conclusions:Efectiveness of school closure on the epidemics varies with the age structure in the population and social contact patterns.School closure should be recommended in the low urbanized regions in China in the infuenza seasons.展开更多
基金funded by the National Institutes of Health grant number HD092286(JPD and JAR)the U.S.Department of Agriculture grant number 2016-09448(JPD)+4 种基金the AMP Core of the Center of Emerging and Zoonotic Infectious Diseases(CEZID)from National Institute of General Medical Sciences(NIGMS)under award number P20GM130448the NIAID supported Centers of Excellence for Infuenza Research and Response(CEIRR,contract number 75N93021C00016the NIAID funded Center of Excellence for Infuenza Research and Surveillance(CEIRS)grant number HHSN272201400006C(JAR)the U.S.Department of Homeland Security grant number DHS2010-ST-061-AG0001(JAR)the Center of Excellence for Emerging and Zoonotic Animal Disease(CEEZAD).
文摘Natural killer T(NKT)cells activated with the glycolipid ligandα-galactosylceramide(α-GalCer)stimulate a wide variety of immune cells that enhance vaccine-mediated immune responses.Several studies have used this approach to adjuvant inactivated and subunit infuenza A virus(IAV)vaccines,including to enhance cross-protective infuenza immunity.However,less is known about whetherα-GalCer can enhance live attenuated infuenza virus(LAIV)vaccines,which usually induce superior heterologous and heterosubtypic immunity compared to non-replicating infuenza vaccines.The current study used the swine infuenza challenge model to assess whetherα-GalCer can enhance cross-protective immune responses elicited by a recombinant H3N2 LAIV vaccine(TX98ΔNS1)encoding a truncated NS1 protein.In one study,weaning pigs were administered the H3N2 TX98ΔNS1 LAIV vaccine with 0,10,50,and 100μg/kg doses ofα-GalCer,and subsequently challenged with a heterologous H3N2 virus.All treatment groups were protected from infection.However,the addition ofα-GalCer appeared to suppress nasal shedding of the LAIV vaccine.In another experiment,pigs vaccinated with the H3N2 LAIV,with or without 50μg/kg ofα-GalCer,were challenged with the heterosubtypic pandemic H1N1 virus.Pigs vaccinated with the LAIV alone generated cross-reactive humoral and cellular responses which blocked virus replication in the airways,and signifcantly decreased virus shedding.On the other hand,combining the vaccine withα-GalCer reduced cross-protective cellular and antibody responses,and resulted in higher virus titers in respiratory tissues.These fndings suggest that:(i)high doses ofα-GalCer impair the replication and nasal shedding of the LAIV vaccine;and(ii)α-GalCer might interfere with heterosubtypic cross-protective immune responses.This research raise concerns that should be considered before trying to use NKT cell agonists as a possible adjuvant approach for LAIV vaccines.
基金funded by grants from the Shenzhen Science and Technology Program(Grant No.KQTD20180411143323605)the National Natural Science Foundation of China(Grant No.82003509)+1 种基金the Natural Science Foundation of Zhejiang Province(Grant No.LQ20H260009)Fundamental Research Funds for the Central Universities.
文摘Background:School closure is a common mitigation strategy during severe infuenza epidemics and pandemics.However,the efectiveness of this strategy remains controversial.In this study,we aimed to explore the efectiveness of school closure on seasonal infuenza epidemics in provincial-level administrative divisions(PLADs)with varying urbanization rates in China.Methods:This study analyzed infuenza surveillance data between 2010 and 2019 provided by the Chinese National Infuenza Center.Taking into consideration the climate,this study included a region with 3 adjacent PLADs in Northern China and another region with 4 adjacent PLADs in Southern China.The efect of school closure on infuenza transmission was evaluated by the reduction of the efective reproductive number of seasonal infuenza during school winter breaks compared with that before school winter breaks.An age-structured Susceptible-Infected-Recovered-Susceptible(SIRS)model was built to model infuenza transmission in diferent levels of urbanization.Parameters were determined using the surveillance data via robust Bayesian method.Results:Between 2010 and 2019,in the less urbanized provinces:Hebei,Zhejiang,Jiangsu and Anhui,during school winter breaks,the efective reproductive number of seasonal infuenza epidemics reduced 14.6%[95%confdential interval(CI):6.2–22.9%],9.6%(95%CI:2.5–16.6%),7.3%(95%CI:0.1–14.4%)and 8.2%(95%CI:1.1–15.3%)respectively.However,in the highly urbanized cities:Beijing,Tianjin and Shanghai,it reduced only 5.2%(95%CI:-0.7–11.2%),4.1%(95%CI:-0.9–9.1%)and 3.9%(95%CI:-1.6–9.4%)respectively.In China,urbanization is associated with decreased proportion of children and increased social contact.According to the SIRS model,both factors could reduce the impact of school closure on seasonal infuenza epidemics,and the proportion of children in the population is thought to be the dominant infuencing factor.Conclusions:Efectiveness of school closure on the epidemics varies with the age structure in the population and social contact patterns.School closure should be recommended in the low urbanized regions in China in the infuenza seasons.
