乙型肝炎病毒(Hepatitis B virus,HBV)感染是全球重大的公共卫生问题,严重损害患者身心健康。我国处于HBV高流行地区,孕产妇普遍易感,母婴传播是儿童早期感染HBV的主要途径,HBV母婴传播综合干预问题值得我们重点关注。本文通过文献回顾...乙型肝炎病毒(Hepatitis B virus,HBV)感染是全球重大的公共卫生问题,严重损害患者身心健康。我国处于HBV高流行地区,孕产妇普遍易感,母婴传播是儿童早期感染HBV的主要途径,HBV母婴传播综合干预问题值得我们重点关注。本文通过文献回顾法,对国内外常见的HBV母婴传播干预策略及其效果进行综述,以期为改进我国综合防治HBV母婴传播提供参考依据。展开更多
目的建立蛋白酶K结合磁珠免疫沉淀提取贝类中甲型肝炎病毒(hepatitis A virus,HAV)的方法,并与国际标准方法(ISO15216—2017)进行比较研究。方法应用高效价的HAV单克隆抗体,采用偶联技术,通过优化参数,建立蛋白酶K结合磁珠免疫沉淀的提...目的建立蛋白酶K结合磁珠免疫沉淀提取贝类中甲型肝炎病毒(hepatitis A virus,HAV)的方法,并与国际标准方法(ISO15216—2017)进行比较研究。方法应用高效价的HAV单克隆抗体,采用偶联技术,通过优化参数,建立蛋白酶K结合磁珠免疫沉淀的提取方法;通过人工预加入103~105 CCID50/mL的4种甲型肝炎活病毒,计算回收率和相对标准偏差(relative standard deviation,RSD),评价方法的提取效果;通过对来自5个产地的4种贝类进行病毒提取和一步法实时荧光定量逆转录PCR(quantitative real-time reverse transcriptase polymerase chainreaction,qRT-PCR)检测,评价方法的适用性。结果HAV单抗效价为1×107,纯度为94.36%,与戊型肝炎病毒、乙型肝炎病毒以及同为小RNA病毒的柯萨奇病毒A16型和肠道病毒A71型均无交叉反应,特异性良好。贝类样品中HAV的平均回收率为22.02%,RSD为0.67%~5.87%,表明该方法对HAV是有效的。与国际标准提取方法相比,在不同浓度下可将HAV检测拷贝数提高10倍以上,显示出良好的剂量效应关系,并且可将不同产地间、不同品种贝类间的检测RSD从4.31%~44.75%和0.61%~29.10%,分别降低至1.76%~6.90%和0.63%~4.80%,有效降低贝类组织中干扰成分的影响。结论该方法较国际标准方法回收率高、抗干扰能力强,具有良好的重现性,提高了贝类等食品中HAV检测灵敏度、可靠性,为贝类等食品安全检测提供了关键的提取手段。展开更多
Objective To evaluate the effect of intranasal immunization with CTA1-DD as mucosal adjuvant combined with H3N2 split vaccine. Methods Mice were immunized intranasally with PBS(negative control), or H3N2 split vaccine...Objective To evaluate the effect of intranasal immunization with CTA1-DD as mucosal adjuvant combined with H3N2 split vaccine. Methods Mice were immunized intranasally with PBS(negative control), or H3N2 split vaccine(3 μg/mouse) alone, or CTA1-DD(5 μg/mouse) alone, or H3N2 split vaccine(3 μg/mouse) plus CTA1-DD(5 μg/mouse). Positive control mice were immunized intramuscularly with H3N2 split vaccine(3 μg/mouse) and alum adjuvant. All the mice were immunized twice, two weeks apart. Then sera and mucosal lavages were collected. The specific HI titers, IgM, IgG, IgA, and IgG subtypes were examined by ELISA. IFN-γ and IL-4 were test by ELISpot. In addition, two weeks after the last immunization, surivival after H3N2 virus lethal challenge was measured. Results H3N2 split vaccine formulated with CTA1-DD could elicit higher Ig M, Ig G and hemagglutination inhibition titers in sera. Furthermore, using CTA1-DD as adjuvant significantly improved mucosal secretory Ig A titers in bronchoalveolar lavages and vaginal lavages. Meanwhile this mucosal adjuvant could enhance Th-1-type responses and induce protective hemagglutination inhibition titers. Notably, the addition of CTA1-DD to split vaccine provided 100% protection against lethal infection by the H3N2 virus. Conclusion CTA1-DD could promote mucosal, humoral and cell-mediated immune responses, which supports the further development of CTA1-DD as a mucosal adjuvant for mucosal vaccines.展开更多
Objective To investigate whether Omicron BA.1 breakthrough infection after receiving the SARS-CoV-2 vaccine could create a strong immunity barrier.Methods Blood samples were collected at two different time points from...Objective To investigate whether Omicron BA.1 breakthrough infection after receiving the SARS-CoV-2 vaccine could create a strong immunity barrier.Methods Blood samples were collected at two different time points from 124 Omicron BA.1 breakthrough infected patients and 124 controls matched for age,gender,and vaccination profile.Live virus-neutralizing antibodies against five SARS-CoV-2 variants,including WT,Gamma,Beta,Delta,and Omicron BA.1,and T-lymphocyte lymphocyte counts in both groups were measured and statistically analyzed.Results The neutralizing antibody titers against five different variants of SARS-CoV-2 were significantly increased in the vaccinated population infected with the Omicron BA.1 variant at 3 months after infection,but mainly increased the antibody level against the WT strain,and the antibody against the Omicron strain was the lowest.The neutralizing antibody level decreased rapidly 6 months after infection.The T-lymphocyte cell counts of patients with mild and moderate disease recovered at 3 months and completely returned to the normal state at 6 months.Conclusion Omicron BA.1 breakthrough infection mainly evoked humoral immune memory in the original strain after vaccination and hardly produced neutralizing antibodies specific to Omicron BA.1.Neutralizing antibodies against the different strains declined rapidly and showed features similar to those of influenza.Thus,T-lymphocytes may play an important role in recovery.展开更多
Objective Long-term seroprotection via the hepatitis A vaccine is essential for the prevention of disease from the hepatitis A virus(HAV).Due to documented difficulties during decade-long follow-ups after receiving va...Objective Long-term seroprotection via the hepatitis A vaccine is essential for the prevention of disease from the hepatitis A virus(HAV).Due to documented difficulties during decade-long follow-ups after receiving vaccines,statistical-modeling approaches have been applied to predict the duration of immune protection.Methods Based on five-year follow-up data from a randomized positive-controlled trial among Chinese children(1–8 years old)following a 0,6 months vaccination schedule,a power-law model accounting for the kinetics of B-cell turnover,as well as a modified power-law model considering a memory-B-cell subpopulation,were fitted to predict the long-term immune responses induced by HAV vaccination(Healive or Havrix).Anti-HAV levels of each individual and seroconversion rates up to 30 years after vaccination were predicted.Results A total of 375 participants who completed the two-dose vaccination were included in the analysis.Both models predicted that,over a life-long period,participants vaccinated with Healive would have close but slightly higher antibody titers than those of participants vaccinated with Havrix.Additionally,consistent with previous studies,more than 90%of participants were predicted to maintain seroconversion for at least 30 years.Moreover,the modified power-law model predicted that the antibody titers would reach a plateau level after nearly 15 years post-vaccination.Conclusions Based on the results of our modeling,Healive may adequately induce long-term immune responses following a 0,6 months vaccination schedule in children via induction of memory B cells to provide stable and durable immune protection.展开更多
The monkeypox virus(mpox virus,MPXV)epidemic in 2022 has posed a significant public health risk.Yet,the evolutionary principles of MPXV remain largely unknown.Here,we examined the evolutionary patterns of protein sequ...The monkeypox virus(mpox virus,MPXV)epidemic in 2022 has posed a significant public health risk.Yet,the evolutionary principles of MPXV remain largely unknown.Here,we examined the evolutionary patterns of protein sequences and codon usage in MPXV.We first demonstrated the signal of positive selection in OPG027,specifically in the CladeⅠlineage of MPXV.Subsequently,we discovered accelerated protein sequence evolution over time in the variants responsible for the 2022 outbreak.Furthermore,we showed strong epistasis between amino acid substitutions located in different genes.The codon adaptation index(CAI)analysis revealed that MPXV genes tended to use more non-preferred codons compared to human genes,and the CAI decreased over time and diverged between clades,with CladeⅠ>Ⅱa andⅡb-A>Ⅱb-B.While the decrease in fatality rate among the three groups aligned with the CAI pattern,it remains unclear whether this correlation was coincidental or if the deoptimization of codon usage in MPXV led to a reduction in fatality rates.This study sheds new light on the mechanisms that govern the evolution of MPXV in human populations.展开更多
Tumor immunotherapy,particularly cancer vaccines,holds promise for combating cancer by harnessing tailored immune responses against malignant cells.However,conventional approaches face challenges in efficiently delive...Tumor immunotherapy,particularly cancer vaccines,holds promise for combating cancer by harnessing tailored immune responses against malignant cells.However,conventional approaches face challenges in efficiently delivering antigens for optimal immune activation.Emulsion adjuvants,like MF59,enhance cellular uptake but struggle to induce robust CD8^(+)T cell responses.Here,we introduce a novel strategy employing a water-in-oil-in-water(W/O/W)multiple Pickering emulsion(mPE)for antigen delivery.The mPE,utilizing biocompatible,pH-sensitive particles,encapsulates antigens within the inner water phase,ensuring enhanced intracellular processing and dictating the intracellular fate of antigens for improved cross-presentation.In vitro and in vivo studies demonstrated that mPEs induced robust dendritic cells activation and antigen cross-presentation,leading to a significantly enhanced immune response.Notably,calcium phosphate-stabilized mPE(CaP-mPE)illustrated the more robust IFN-γ^(+)T cell responses.In comparison with traditional surfactant-stabilized multiple emulsions,CaP-mPE significantly inhibit tumor growth and effectively prolong the survival of tumor-bearing mice.This innovative approach offers a promising avenue for the development of effective cancer vaccines with potent cellular immune responses.展开更多
Varicella-zoster is a highly communicable virus that can be transmitted through the airborne route.About one quarter of people are infected with this virus.Previous studies have described the structure of A-capsid and...Varicella-zoster is a highly communicable virus that can be transmitted through the airborne route.About one quarter of people are infected with this virus.Previous studies have described the structure of A-capsid and a blurred reconstruction of the C-capsid with icosahedral symmetry.In this study,we have determined the more precise detailed structures of the varicella-zoster virus(VZV)B-and C-capsid in icosahedral symmetry using a combination of block-based reconstruction and symmetry relaxation strategies.In addition,we are reporting structural details of the portal vertex reconstructions in five-fold symmetry and portal reconstructions in twelve-fold symmetry.The structures unveil the basis for the high thermal stability of the VZV capsid.The conformational flexibility of structural elements of the capsid plays a role in the assembly of the capsid and drives processes critical for the viral life cycle.The results of the study open up new avenues for the development of drugs against a highly prevalent and contagious pathogen.展开更多
目的评价采用检测阴性设计(Test-negative design,TND)病例对照研究评价肠道病毒71型(Enterovirus type 71,EV71)灭活疫苗保护效果(Vaccine effectiveness,VE)的可行性。方法运用TND病例对照研究对一项EV71疫苗VE随机对照试验(Randomize...目的评价采用检测阴性设计(Test-negative design,TND)病例对照研究评价肠道病毒71型(Enterovirus type 71,EV71)灭活疫苗保护效果(Vaccine effectiveness,VE)的可行性。方法运用TND病例对照研究对一项EV71疫苗VE随机对照试验(Randomized controlled trial,RCT)相关数据再分析,采用2种分析集和3种病例对照分组方式共6种组合分析集,分别计算EV71疫苗对EV71感染所致手足口病(Hand,foot and mouth disease,HFMD)、住院和所有疾病的VE及其与RCT研究VE的差值。结果在TND病例对照研究中,当以EV71阴性和其他EV阳性为对照时,采用六种组合分析集计算的EV71疫苗对HFMD、住院、所有疾病的VE分别在93.6%-93.9%、100%-100%、86.8%-87.8%之间,比RCT的VE分别低0.6-0.8、0.0-0.0、0.2-0.5个百分点;当以EV71阴性和其他EV泛阴性为对照时,EV71疫苗对HFMD和所有疾病的VE分别在93.8%-94.1%和86.9%-87.7%之间,比RCT的VE分别低0.4-0.6和0.2-0.5个百分点;当以EV71阴性为对照时,EV71疫苗对HFMD、住院、所有疾病的VE分别在93.7%-93.9%、100%-100%、86.9%-87.8%之间,比RCT的VE分别低0.6-0.8、0.0-0.0、0.1-0.4个百分点。结论采用TND病例对照研究计算的EV71疫苗VE与RCT结果基本一致;该方法可应用于评价EV71疫苗在真实世界中的VE。展开更多
基金国家卫生健康委-联合国儿童基金会消除艾滋病、梅毒和乙肝母婴传播试点项目(501 HealthNutrition and Wash)。
文摘乙型肝炎病毒(Hepatitis B virus,HBV)感染是全球重大的公共卫生问题,严重损害患者身心健康。我国处于HBV高流行地区,孕产妇普遍易感,母婴传播是儿童早期感染HBV的主要途径,HBV母婴传播综合干预问题值得我们重点关注。本文通过文献回顾法,对国内外常见的HBV母婴传播干预策略及其效果进行综述,以期为改进我国综合防治HBV母婴传播提供参考依据。
基金supported by the Chinese National Science and Technology Major Project for Important Infectious Diseases Control and Prevention [Grant No.2017ZX10105015001002]
文摘Objective To evaluate the effect of intranasal immunization with CTA1-DD as mucosal adjuvant combined with H3N2 split vaccine. Methods Mice were immunized intranasally with PBS(negative control), or H3N2 split vaccine(3 μg/mouse) alone, or CTA1-DD(5 μg/mouse) alone, or H3N2 split vaccine(3 μg/mouse) plus CTA1-DD(5 μg/mouse). Positive control mice were immunized intramuscularly with H3N2 split vaccine(3 μg/mouse) and alum adjuvant. All the mice were immunized twice, two weeks apart. Then sera and mucosal lavages were collected. The specific HI titers, IgM, IgG, IgA, and IgG subtypes were examined by ELISA. IFN-γ and IL-4 were test by ELISpot. In addition, two weeks after the last immunization, surivival after H3N2 virus lethal challenge was measured. Results H3N2 split vaccine formulated with CTA1-DD could elicit higher Ig M, Ig G and hemagglutination inhibition titers in sera. Furthermore, using CTA1-DD as adjuvant significantly improved mucosal secretory Ig A titers in bronchoalveolar lavages and vaginal lavages. Meanwhile this mucosal adjuvant could enhance Th-1-type responses and induce protective hemagglutination inhibition titers. Notably, the addition of CTA1-DD to split vaccine provided 100% protection against lethal infection by the H3N2 virus. Conclusion CTA1-DD could promote mucosal, humoral and cell-mediated immune responses, which supports the further development of CTA1-DD as a mucosal adjuvant for mucosal vaccines.
基金funded by the Emergency prevention and cure Program of COVID-19[22ZXGBSY00010]Tianjin Medical Key Discipline Project[TJYXZDXK-50A]sponsored by Tianjin Municipal Science and Technology Bureau and Tianjin Municipal Health Commission,respectively.
文摘Objective To investigate whether Omicron BA.1 breakthrough infection after receiving the SARS-CoV-2 vaccine could create a strong immunity barrier.Methods Blood samples were collected at two different time points from 124 Omicron BA.1 breakthrough infected patients and 124 controls matched for age,gender,and vaccination profile.Live virus-neutralizing antibodies against five SARS-CoV-2 variants,including WT,Gamma,Beta,Delta,and Omicron BA.1,and T-lymphocyte lymphocyte counts in both groups were measured and statistically analyzed.Results The neutralizing antibody titers against five different variants of SARS-CoV-2 were significantly increased in the vaccinated population infected with the Omicron BA.1 variant at 3 months after infection,but mainly increased the antibody level against the WT strain,and the antibody against the Omicron strain was the lowest.The neutralizing antibody level decreased rapidly 6 months after infection.The T-lymphocyte cell counts of patients with mild and moderate disease recovered at 3 months and completely returned to the normal state at 6 months.Conclusion Omicron BA.1 breakthrough infection mainly evoked humoral immune memory in the original strain after vaccination and hardly produced neutralizing antibodies specific to Omicron BA.1.Neutralizing antibodies against the different strains declined rapidly and showed features similar to those of influenza.Thus,T-lymphocytes may play an important role in recovery.
基金sub-project of National Major Scientific and Technological Special Project of China for‘Significant New Drugs Development’[2015ZX09501008-004]。
文摘Objective Long-term seroprotection via the hepatitis A vaccine is essential for the prevention of disease from the hepatitis A virus(HAV).Due to documented difficulties during decade-long follow-ups after receiving vaccines,statistical-modeling approaches have been applied to predict the duration of immune protection.Methods Based on five-year follow-up data from a randomized positive-controlled trial among Chinese children(1–8 years old)following a 0,6 months vaccination schedule,a power-law model accounting for the kinetics of B-cell turnover,as well as a modified power-law model considering a memory-B-cell subpopulation,were fitted to predict the long-term immune responses induced by HAV vaccination(Healive or Havrix).Anti-HAV levels of each individual and seroconversion rates up to 30 years after vaccination were predicted.Results A total of 375 participants who completed the two-dose vaccination were included in the analysis.Both models predicted that,over a life-long period,participants vaccinated with Healive would have close but slightly higher antibody titers than those of participants vaccinated with Havrix.Additionally,consistent with previous studies,more than 90%of participants were predicted to maintain seroconversion for at least 30 years.Moreover,the modified power-law model predicted that the antibody titers would reach a plateau level after nearly 15 years post-vaccination.Conclusions Based on the results of our modeling,Healive may adequately induce long-term immune responses following a 0,6 months vaccination schedule in children via induction of memory B cells to provide stable and durable immune protection.
基金We thank the researchers who generated and shared the sequencing data in the NCBI(Table S4)and GISAID(https://www.gisaid.org/)(Table S5),on which this research is basedThis work is supported by the National Key R&D Projects of China(Grant Nos.2021YFC2301300,2022YFC2304100,and 2022YFC2303401)+2 种基金the National Natural Science Foundation of China(Grant No.82241080)the Beijing Natural Science Foundation,China(Grant No.L222009)the SLS-Qidong Innovation Fund,China,and the Beijing Postdoctoral Research Foundation,China(Grant No.2023-ZZ-018).
文摘The monkeypox virus(mpox virus,MPXV)epidemic in 2022 has posed a significant public health risk.Yet,the evolutionary principles of MPXV remain largely unknown.Here,we examined the evolutionary patterns of protein sequences and codon usage in MPXV.We first demonstrated the signal of positive selection in OPG027,specifically in the CladeⅠlineage of MPXV.Subsequently,we discovered accelerated protein sequence evolution over time in the variants responsible for the 2022 outbreak.Furthermore,we showed strong epistasis between amino acid substitutions located in different genes.The codon adaptation index(CAI)analysis revealed that MPXV genes tended to use more non-preferred codons compared to human genes,and the CAI decreased over time and diverged between clades,with CladeⅠ>Ⅱa andⅡb-A>Ⅱb-B.While the decrease in fatality rate among the three groups aligned with the CAI pattern,it remains unclear whether this correlation was coincidental or if the deoptimization of codon usage in MPXV led to a reduction in fatality rates.This study sheds new light on the mechanisms that govern the evolution of MPXV in human populations.
基金the National Key R&D Program of China(grant No.2022YFE0202500)Distinguished Young Scholars of the National Natural Science Foundation of China(grant No.T2222022)+2 种基金National Key Research and Development Program of China(grant No.2021YFC2302400,2021YFC2302600)Major Program of the National Natural Science Foundation of China(grant No.T2394503,T2394501)Key Project of the National Natural Science Foundation of China(grant No.32030062),CAS Project for。
文摘Tumor immunotherapy,particularly cancer vaccines,holds promise for combating cancer by harnessing tailored immune responses against malignant cells.However,conventional approaches face challenges in efficiently delivering antigens for optimal immune activation.Emulsion adjuvants,like MF59,enhance cellular uptake but struggle to induce robust CD8^(+)T cell responses.Here,we introduce a novel strategy employing a water-in-oil-in-water(W/O/W)multiple Pickering emulsion(mPE)for antigen delivery.The mPE,utilizing biocompatible,pH-sensitive particles,encapsulates antigens within the inner water phase,ensuring enhanced intracellular processing and dictating the intracellular fate of antigens for improved cross-presentation.In vitro and in vivo studies demonstrated that mPEs induced robust dendritic cells activation and antigen cross-presentation,leading to a significantly enhanced immune response.Notably,calcium phosphate-stabilized mPE(CaP-mPE)illustrated the more robust IFN-γ^(+)T cell responses.In comparison with traditional surfactant-stabilized multiple emulsions,CaP-mPE significantly inhibit tumor growth and effectively prolong the survival of tumor-bearing mice.This innovative approach offers a promising avenue for the development of effective cancer vaccines with potent cellular immune responses.
基金supported by the Strategic Priority Research Program (XDB29010000)National Key Research and Development Program (2018YFA0900801)+5 种基金National Science Foundation Grants 32200135 and 12034006supported by National Science Fund for Distinguished Young Scholar (No.32325004)the NSFS Innovative Research Group (No.81921005)supported by the Young Elite Scientists Sponsorship Program by CAST (2022QNRC001)the Youth Innovation Promotion Association of CAS grantsupported by the Special Research Assistant Project of the Chinese Academy of Sciences.
文摘Varicella-zoster is a highly communicable virus that can be transmitted through the airborne route.About one quarter of people are infected with this virus.Previous studies have described the structure of A-capsid and a blurred reconstruction of the C-capsid with icosahedral symmetry.In this study,we have determined the more precise detailed structures of the varicella-zoster virus(VZV)B-and C-capsid in icosahedral symmetry using a combination of block-based reconstruction and symmetry relaxation strategies.In addition,we are reporting structural details of the portal vertex reconstructions in five-fold symmetry and portal reconstructions in twelve-fold symmetry.The structures unveil the basis for the high thermal stability of the VZV capsid.The conformational flexibility of structural elements of the capsid plays a role in the assembly of the capsid and drives processes critical for the viral life cycle.The results of the study open up new avenues for the development of drugs against a highly prevalent and contagious pathogen.
文摘目的评价采用检测阴性设计(Test-negative design,TND)病例对照研究评价肠道病毒71型(Enterovirus type 71,EV71)灭活疫苗保护效果(Vaccine effectiveness,VE)的可行性。方法运用TND病例对照研究对一项EV71疫苗VE随机对照试验(Randomized controlled trial,RCT)相关数据再分析,采用2种分析集和3种病例对照分组方式共6种组合分析集,分别计算EV71疫苗对EV71感染所致手足口病(Hand,foot and mouth disease,HFMD)、住院和所有疾病的VE及其与RCT研究VE的差值。结果在TND病例对照研究中,当以EV71阴性和其他EV阳性为对照时,采用六种组合分析集计算的EV71疫苗对HFMD、住院、所有疾病的VE分别在93.6%-93.9%、100%-100%、86.8%-87.8%之间,比RCT的VE分别低0.6-0.8、0.0-0.0、0.2-0.5个百分点;当以EV71阴性和其他EV泛阴性为对照时,EV71疫苗对HFMD和所有疾病的VE分别在93.8%-94.1%和86.9%-87.7%之间,比RCT的VE分别低0.4-0.6和0.2-0.5个百分点;当以EV71阴性为对照时,EV71疫苗对HFMD、住院、所有疾病的VE分别在93.7%-93.9%、100%-100%、86.9%-87.8%之间,比RCT的VE分别低0.6-0.8、0.0-0.0、0.1-0.4个百分点。结论采用TND病例对照研究计算的EV71疫苗VE与RCT结果基本一致;该方法可应用于评价EV71疫苗在真实世界中的VE。
