Background: Omicron JN.1 has become the dominant SARS-CoV-2 variant in recent months. JN.1 has the highest number of amino acid mutations in its receptor binding domain (RBD) and has acquired a hallmark L455S mutation...Background: Omicron JN.1 has become the dominant SARS-CoV-2 variant in recent months. JN.1 has the highest number of amino acid mutations in its receptor binding domain (RBD) and has acquired a hallmark L455S mutation. The immune evasion capability of JN.1 is a subject of scientific investigation. The US CDC used SGTF of TaqPath COVID-19 Combo Kit RT-qPCR as proxy indicator of JN.1 infections for evaluation of the effectiveness of updated monovalent XBB.1.5 COVID-19 vaccines against JN.1 and recommended that all persons aged ≥ 6 months should receive an updated COVID-19 vaccine dose. Objective: Recommend Sanger sequencing instead of proxy indicator to diagnose JN.1 infections to generate the data based on which guidelines are made to direct vaccination policies. Methods: The RNA in nasopharyngeal swab specimens from patients with clinical respiratory infection was subjected to nested RT-PCR, targeting a 398-base segment of the N-gene and a 445-base segment of the RBD of SARS-CoV-2 for amplification. The nested PCR amplicons were sequenced. The DNA sequences were analyzed for amino acid mutations. Results: The N-gene sequence showed R203K, G204R and Q229K, the 3 mutations associated with Omicron BA.2.86 (+JN.1). The RBD sequence showed 24 of the 26 known amino acid mutations, including the hallmark L455S mutation for JN.1 and the V483del for BA.2.86 lineage. Conclusions: Sanger sequencing of a 445-base segment of the SARS-CoV-2 RBD is useful for accurate determination of emerging variants. The CDC may consider using Sanger sequencing of the RBD to diagnose JN.1 infections for statistical analysis in making vaccination policies.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
Periodically updating coronavirus disease 19(COVID-19)vaccines that offer broad-spectrum protection is needed giventhe strong immune evasion by the circulating omicron sublineages.The effectiveness of prototype and BA...Periodically updating coronavirus disease 19(COVID-19)vaccines that offer broad-spectrum protection is needed giventhe strong immune evasion by the circulating omicron sublineages.The effectiveness of prototype and BA.4/5-containing bivalent mRNA vaccines is reduced when XBB subvariants predominate.We initiated an observer-blinded,threearms study in 376 patients in Chinese individuals aged from 18 to 55 years old who had previously received three dosesCOVID-19 vaccine.Immunogenicity in terms of neutralizing antibodies elicited by a 30-mg dose of XBB.1.5-containingbivalent vaccine(RQ3027),a 30-mg dose of BA.2/BA.5-Alpha/Beta bivalent vaccine(RQ3025)and their precedent 30-mg Alpha/Beta(combined mutations)monovalent mRNA vaccine(RQ3013)and safety are primary and secondary endpoints,respectively.We recorded prescribed COVID-19 cases to explore the preliminary efficacy of three vaccines.RQ3027 and RQ3025 boosters elicited superior neutralizing antibodies(NAbs)against XBB.1.5,XBB.1.16,XBB.1.9.1,and JN.1 compared to RQ3013 at day 14 in participants without SARS-CoV-2 infection.All study vaccines were welltolerated without serious adverse reactions identified.The incidence rates per 1000 person-years of COVID-19 casesduring the 2nd-19th week after randomization were lowest in RQ3027.Overall,our data show that XBB.1.5-containingbivalent booster generated superior immunogenicity and better protection against newer severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)variants compared to BA.2/BA.5-containing bivalent and Alpha/Beta monovalentwith no new safety concerns.展开更多
The twenty-first century has already recorded more than ten major epidemics or pandemics of viral disease,including the devastating COVID-19.Novel effective antivirals with broad-spectrum coverage are urgently needed....The twenty-first century has already recorded more than ten major epidemics or pandemics of viral disease,including the devastating COVID-19.Novel effective antivirals with broad-spectrum coverage are urgently needed.Herein,we reported a novel broad-spectrum antiviral compound PAC5.Oral administration of PAC5 eliminated HBV cccDNA and reduced the large antigen load in distinct mouse models of HBV infection.Strikingly,oral administration of PAC5 in a hamster model of SARS-CoV-2 omicron(BA.1)infection significantly decreases viral loads and attenuates lung inflammation.Mechanistically,PAC5 binds to a pocket near Asp49 in the RNA recognition motif of hnRNPA2B1.PAC5-bound hnRNPA2B1 is extensively activated and translocated to the cytoplasm where it initiates the TBK1-IRF3 pathway,leading to the production of type I IFNs with antiviral activity.Our results indicate that PAC5 is a novel small-molecule agonist of hnRNPA2B1,which may have a role in dealing with emerging infectious diseases now and in the future.展开更多
新型冠状病毒Omicron变异株出现之后,在全球暴发流行过程中不断进化出传播速度更快、免疫逃逸能力更强的进化分支,为了探究BA.1变异株在全球暴发流行的特征及刺突蛋白(Spike,S)基因的进化特征,本研究对其全基因序列的全球报告情况和S基...新型冠状病毒Omicron变异株出现之后,在全球暴发流行过程中不断进化出传播速度更快、免疫逃逸能力更强的进化分支,为了探究BA.1变异株在全球暴发流行的特征及刺突蛋白(Spike,S)基因的进化特征,本研究对其全基因序列的全球报告情况和S基因的进化特征进行了分析。本文通过全球共享流感数据倡议组织(Global Initiative of Sharing All Influenza Data,GISAID)获取Omicron BA.1系列变异株的全基因序列信息,分析BA.1系列变异株S基因氨基酸突变并构建系统进化树和进行贝叶斯系统进化分析。本研究提示全球约有1.2亿人被BA.1系列变异株感染,全球提交的BA.1系列变异株序列数在其出现2个月后达到高峰,5个月后占新型冠状病毒的比例下降到4.38%,累计提交BA.1全基因序列最多的区域是欧洲、美洲;截止2022年10月,BA.1系列变异株中序列提交数占绝对优势的是BA.1.1(42.07%),其次是BA.1(18.81%)。对S基因的氨基酸变异分析显示BA.1有56个进化分支,其中48个分支稳定遗传了Omicron原始株S蛋白中的18个氨基酸突变位点。对BA.1 S基因的进化分析显示其共同祖先形成时间(TMRCA)可追溯到2020年11月,S基因平均碱基替代速率为9.36×10^(-4)替换/位点/年,2021年3月BA.1流行过程中形成两个独立簇,推测G346K、G446S突变位点可能是提高病毒传播力的主要突变。本研究分析了BA.1系列变异株的流行及进化特征,其在短时间内迅速替代Delta毒株,成为全球绝对优势流行株,并有迅速被BA.2亚型代替的潜力。此外,BA.1在全球3~4个月的流行中,逐渐演变出56个进化分支,在全球流行时间短、出现部分稳定遗传的氨基酸突变、进化速率较快。因此,需密切关注Omicron系列变异株基因序列变异变迁、监测新增突变位点,及时研判新变异株的传播力、免疫逃逸能力和致病力。展开更多
文摘Background: Omicron JN.1 has become the dominant SARS-CoV-2 variant in recent months. JN.1 has the highest number of amino acid mutations in its receptor binding domain (RBD) and has acquired a hallmark L455S mutation. The immune evasion capability of JN.1 is a subject of scientific investigation. The US CDC used SGTF of TaqPath COVID-19 Combo Kit RT-qPCR as proxy indicator of JN.1 infections for evaluation of the effectiveness of updated monovalent XBB.1.5 COVID-19 vaccines against JN.1 and recommended that all persons aged ≥ 6 months should receive an updated COVID-19 vaccine dose. Objective: Recommend Sanger sequencing instead of proxy indicator to diagnose JN.1 infections to generate the data based on which guidelines are made to direct vaccination policies. Methods: The RNA in nasopharyngeal swab specimens from patients with clinical respiratory infection was subjected to nested RT-PCR, targeting a 398-base segment of the N-gene and a 445-base segment of the RBD of SARS-CoV-2 for amplification. The nested PCR amplicons were sequenced. The DNA sequences were analyzed for amino acid mutations. Results: The N-gene sequence showed R203K, G204R and Q229K, the 3 mutations associated with Omicron BA.2.86 (+JN.1). The RBD sequence showed 24 of the 26 known amino acid mutations, including the hallmark L455S mutation for JN.1 and the V483del for BA.2.86 lineage. Conclusions: Sanger sequencing of a 445-base segment of the SARS-CoV-2 RBD is useful for accurate determination of emerging variants. The CDC may consider using Sanger sequencing of the RBD to diagnose JN.1 infections for statistical analysis in making vaccination policies.
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supported by a grant(2023YFC2307600,to Z.J.Z.)from the Na-tional Key Research and Development Program of Chinaa grant(202102AA100051,to Z.J.Z.)from the Yunnan Provincial Sci-ence and Technology Department,China+2 种基金a grant(H-2018102,to J.W.)from the High-level Health Technical Personnel Project of Yunnan Province,Chinaa grant(2022SCP001,to Z.J.Z.)from the Spring City Plan:The High-level Talent Promotion and Training Project of Kunmingand a grant(32371000,to C.M.L.)from the National Natural Science Foundation of China.
文摘Periodically updating coronavirus disease 19(COVID-19)vaccines that offer broad-spectrum protection is needed giventhe strong immune evasion by the circulating omicron sublineages.The effectiveness of prototype and BA.4/5-containing bivalent mRNA vaccines is reduced when XBB subvariants predominate.We initiated an observer-blinded,threearms study in 376 patients in Chinese individuals aged from 18 to 55 years old who had previously received three dosesCOVID-19 vaccine.Immunogenicity in terms of neutralizing antibodies elicited by a 30-mg dose of XBB.1.5-containingbivalent vaccine(RQ3027),a 30-mg dose of BA.2/BA.5-Alpha/Beta bivalent vaccine(RQ3025)and their precedent 30-mg Alpha/Beta(combined mutations)monovalent mRNA vaccine(RQ3013)and safety are primary and secondary endpoints,respectively.We recorded prescribed COVID-19 cases to explore the preliminary efficacy of three vaccines.RQ3027 and RQ3025 boosters elicited superior neutralizing antibodies(NAbs)against XBB.1.5,XBB.1.16,XBB.1.9.1,and JN.1 compared to RQ3013 at day 14 in participants without SARS-CoV-2 infection.All study vaccines were welltolerated without serious adverse reactions identified.The incidence rates per 1000 person-years of COVID-19 casesduring the 2nd-19th week after randomization were lowest in RQ3027.Overall,our data show that XBB.1.5-containingbivalent booster generated superior immunogenicity and better protection against newer severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)variants compared to BA.2/BA.5-containing bivalent and Alpha/Beta monovalentwith no new safety concerns.
基金supported by the National Natural Science Foundation of China(Grant Nos.31960093,81973210,81873872,82071781,32160153)the Natural Science Foundation of Yunnan Province(Grant Nos.202001BC070001,202102AA100053,202105AD160008,202207AA110003)the Innovation Team of Chronic Kidney Disease with Integrated Traditional Chinese and Western Medicine(No.2019KCXTD014).
文摘The twenty-first century has already recorded more than ten major epidemics or pandemics of viral disease,including the devastating COVID-19.Novel effective antivirals with broad-spectrum coverage are urgently needed.Herein,we reported a novel broad-spectrum antiviral compound PAC5.Oral administration of PAC5 eliminated HBV cccDNA and reduced the large antigen load in distinct mouse models of HBV infection.Strikingly,oral administration of PAC5 in a hamster model of SARS-CoV-2 omicron(BA.1)infection significantly decreases viral loads and attenuates lung inflammation.Mechanistically,PAC5 binds to a pocket near Asp49 in the RNA recognition motif of hnRNPA2B1.PAC5-bound hnRNPA2B1 is extensively activated and translocated to the cytoplasm where it initiates the TBK1-IRF3 pathway,leading to the production of type I IFNs with antiviral activity.Our results indicate that PAC5 is a novel small-molecule agonist of hnRNPA2B1,which may have a role in dealing with emerging infectious diseases now and in the future.
文摘新型冠状病毒Omicron变异株出现之后,在全球暴发流行过程中不断进化出传播速度更快、免疫逃逸能力更强的进化分支,为了探究BA.1变异株在全球暴发流行的特征及刺突蛋白(Spike,S)基因的进化特征,本研究对其全基因序列的全球报告情况和S基因的进化特征进行了分析。本文通过全球共享流感数据倡议组织(Global Initiative of Sharing All Influenza Data,GISAID)获取Omicron BA.1系列变异株的全基因序列信息,分析BA.1系列变异株S基因氨基酸突变并构建系统进化树和进行贝叶斯系统进化分析。本研究提示全球约有1.2亿人被BA.1系列变异株感染,全球提交的BA.1系列变异株序列数在其出现2个月后达到高峰,5个月后占新型冠状病毒的比例下降到4.38%,累计提交BA.1全基因序列最多的区域是欧洲、美洲;截止2022年10月,BA.1系列变异株中序列提交数占绝对优势的是BA.1.1(42.07%),其次是BA.1(18.81%)。对S基因的氨基酸变异分析显示BA.1有56个进化分支,其中48个分支稳定遗传了Omicron原始株S蛋白中的18个氨基酸突变位点。对BA.1 S基因的进化分析显示其共同祖先形成时间(TMRCA)可追溯到2020年11月,S基因平均碱基替代速率为9.36×10^(-4)替换/位点/年,2021年3月BA.1流行过程中形成两个独立簇,推测G346K、G446S突变位点可能是提高病毒传播力的主要突变。本研究分析了BA.1系列变异株的流行及进化特征,其在短时间内迅速替代Delta毒株,成为全球绝对优势流行株,并有迅速被BA.2亚型代替的潜力。此外,BA.1在全球3~4个月的流行中,逐渐演变出56个进化分支,在全球流行时间短、出现部分稳定遗传的氨基酸突变、进化速率较快。因此,需密切关注Omicron系列变异株基因序列变异变迁、监测新增突变位点,及时研判新变异株的传播力、免疫逃逸能力和致病力。
