Pub Date : 2024-12-01Epub Date: 2024-05-15DOI: 10.1080/22221751.2024.2343907
Jieshi Yu, Zhenyu Wen, Wanke Hu, Mingwang Chen, Yuanlong Zhang, Shasha Liu, Gang Wang, Zhao Wang, Dan Wang, Shao-Lun Zhai, Wen-Kang Wei, Tianyu Li, Ming Liao
Influenza D virus (IDV) plays an important role in the bovine respiratory disease (BRD) complex. Its potential for the zoonotic transmission is of particular concern. In China, IDV has previously been identified in agricultural animals by molecular surveys with no live virus isolates reported. In this study, live IDVs were successfully isolated from cattle in China, which prompted us to further investigate the national prevalence, antigenic property, and infection biology of the virus. IDV RNA was detected in 11.1% (51/460) of cattle throughout the country in 2022-2023. Moreover, we conducted the first IDV serosurveillance in China, revealing a high seroprevalence (91.4%, 393/430) of IDV in cattle during the 2022-2023 winter season. Notably, all the 16 provinces from which cattle originated possessed seropositive animals, and 3 of them displayed the 100% IDV-seropositivity rate. In contrast, a very low seroprevalence of IDV was observed in pigs (3%, 3/100) and goats (1%, 1/100) during the same period of investigation. Furthermore, besides D/Yama2019 lineage-like IDVs, we discovered the D/660 lineage-like IDV in Chinese cattle, which has not been detected to date in Asia. Finally, the Chinese IDVs replicated robustly in diverse cell lines but less efficiently in the swine cell line. Considering the nationwide distribution, high seroprevalence, and appreciably genetic diversity, further studies are required to fully evaluate the risk of Chinese IDVs for both animal and human health in China, which can be evidently facilitated by IDV isolates reported in this study.
{"title":"Influenza D virus infection in China, 2022-2023.","authors":"Jieshi Yu, Zhenyu Wen, Wanke Hu, Mingwang Chen, Yuanlong Zhang, Shasha Liu, Gang Wang, Zhao Wang, Dan Wang, Shao-Lun Zhai, Wen-Kang Wei, Tianyu Li, Ming Liao","doi":"10.1080/22221751.2024.2343907","DOIUrl":"10.1080/22221751.2024.2343907","url":null,"abstract":"<p><p>Influenza D virus (IDV) plays an important role in the bovine respiratory disease (BRD) complex. Its potential for the zoonotic transmission is of particular concern. In China, IDV has previously been identified in agricultural animals by molecular surveys with no live virus isolates reported. In this study, live IDVs were successfully isolated from cattle in China, which prompted us to further investigate the national prevalence, antigenic property, and infection biology of the virus. IDV RNA was detected in 11.1% (51/460) of cattle throughout the country in 2022-2023. Moreover, we conducted the first IDV serosurveillance in China, revealing a high seroprevalence (91.4%, 393/430) of IDV in cattle during the 2022-2023 winter season. Notably, all the 16 provinces from which cattle originated possessed seropositive animals, and 3 of them displayed the 100% IDV-seropositivity rate. In contrast, a very low seroprevalence of IDV was observed in pigs (3%, 3/100) and goats (1%, 1/100) during the same period of investigation. Furthermore, besides D/Yama2019 lineage-like IDVs, we discovered the D/660 lineage-like IDV in Chinese cattle, which has not been detected to date in Asia. Finally, the Chinese IDVs replicated robustly in diverse cell lines but less efficiently in the swine cell line. Considering the nationwide distribution, high seroprevalence, and appreciably genetic diversity, further studies are required to fully evaluate the risk of Chinese IDVs for both animal and human health in China, which can be evidently facilitated by IDV isolates reported in this study.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":null,"pages":null},"PeriodicalIF":13.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11097708/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140911657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01Epub Date: 2023-12-30DOI: 10.1080/22221751.2023.2281355
Jia-Wei Xu, Bu-Sen Wang, Ping Gao, Hai-Tao Huang, Fei-Yu Wang, Wei Qiu, Yuan-Yuan Zhang, Yu Xu, Jin-Bo Gou, Lin-Ling Yu, Xuan Liu, Rui-Jie Wang, Tao Zhu, Li-Hua Hou, Qing- Wang
Vaccination strategies that can induce a broad spectrum immune response are important to enhance protection against SARS-CoV-2 variants. We conducted a randomized, double-blind and parallel controlled trial to evaluate the safety and immunogenicity of the bivalent (5×1010viral particles) and B.1.1.529 variant (5×1010viral particles) adenovirus type-5 (Ad5) vectored COVID-19 vaccines administrated via inhalation. 451 eligible subjects aged 18 years and older who had been vaccinated with three doses inactivated COVID-19 vaccines were randomly assigned to inhale one dose of either B.1.1.529 variant Ad5 vectored COVID-19 vaccine (Ad5-nCoVO-IH group, N=150), bivalent Ad5 vectored COVID-19 vaccine (Ad5-nCoV/O-IH group, N=151), or Ad5 vectored COVID-19 vaccine (5×1010viral particles; Ad5-nCoV-IH group, N=150). Adverse reactions reported by 37 (24.67%) participants in the Ad5-nCoVO-IH group, 28 (18.54%) in the Ad5-nCoV/O-IH group, and 26 (17.33%) in the Ad5-nCoV-IH group with mainly mild to moderate dry mouth, oropharyngeal pain, headache, myalgia, cough, fever and fatigue. No serious adverse events related to the vaccine were reported. Investigational vaccines were immunogenic, with significant difference in the GMTs of neutralizing antibodies against Omicron BA.1 between Ad5-nCoV/O-IH (43.70) and Ad5-nCoV-IH (29.25) at 28 days after vaccination (P=0.0238). The seroconversion rates of neutralizing antibodies against BA.1 in Ad5-nCoVO-IH, Ad5-nCoV/O-IH, and Ad5-nCoV-IH groups were 56.00%, 59.60% and 48.67% with no significant difference among the groups. Overall, the investigational vaccines were demonstrated to be safe and well tolerated in adults, and was highly effective in inducing mucosal immunities in addition to humoral and cellular immune responses defending against SARS-CoV-2 variants.Trial registration: Chictr.org identifier: ChiCTR2200063996.
{"title":"Safety and immunogenicity of heterologous boosting with orally administered aerosolized bivalent adenovirus type-5 vectored COVID-19 vaccine and B.1.1.529 variant adenovirus type-5 vectored COVID-19 vaccine in adults 18 years and older: a randomized, double blinded, parallel controlled trial.","authors":"Jia-Wei Xu, Bu-Sen Wang, Ping Gao, Hai-Tao Huang, Fei-Yu Wang, Wei Qiu, Yuan-Yuan Zhang, Yu Xu, Jin-Bo Gou, Lin-Ling Yu, Xuan Liu, Rui-Jie Wang, Tao Zhu, Li-Hua Hou, Qing- Wang","doi":"10.1080/22221751.2023.2281355","DOIUrl":"10.1080/22221751.2023.2281355","url":null,"abstract":"<p><p>Vaccination strategies that can induce a broad spectrum immune response are important to enhance protection against SARS-CoV-2 variants. We conducted a randomized, double-blind and parallel controlled trial to evaluate the safety and immunogenicity of the bivalent (5×10<sup>10</sup>viral particles) and B.1.1.529 variant (5×10<sup>10</sup>viral particles) adenovirus type-5 (Ad5) vectored COVID-19 vaccines administrated via inhalation. 451 eligible subjects aged 18 years and older who had been vaccinated with three doses inactivated COVID-19 vaccines were randomly assigned to inhale one dose of either B.1.1.529 variant Ad5 vectored COVID-19 vaccine (Ad5-nCoVO-IH group, N=150), bivalent Ad5 vectored COVID-19 vaccine (Ad5-nCoV/O-IH group, N=151), or Ad5 vectored COVID-19 vaccine (5×10<sup>10</sup>viral particles; Ad5-nCoV-IH group, N=150). Adverse reactions reported by 37 (24.67%) participants in the Ad5-nCoVO-IH group, 28 (18.54%) in the Ad5-nCoV/O-IH group, and 26 (17.33%) in the Ad5-nCoV-IH group with mainly mild to moderate dry mouth, oropharyngeal pain, headache, myalgia, cough, fever and fatigue. No serious adverse events related to the vaccine were reported. Investigational vaccines were immunogenic, with significant difference in the GMTs of neutralizing antibodies against Omicron BA.1 between Ad5-nCoV/O-IH (43.70) and Ad5-nCoV-IH (29.25) at 28 days after vaccination (P=0.0238). The seroconversion rates of neutralizing antibodies against BA.1 in Ad5-nCoVO-IH, Ad5-nCoV/O-IH, and Ad5-nCoV-IH groups were 56.00%, 59.60% and 48.67% with no significant difference among the groups. Overall, the investigational vaccines were demonstrated to be safe and well tolerated in adults, and was highly effective in inducing mucosal immunities in addition to humoral and cellular immune responses defending against SARS-CoV-2 variants.Trial registration: Chictr.org identifier: ChiCTR2200063996.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":null,"pages":null},"PeriodicalIF":13.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11025474/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71479447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01Epub Date: 2024-06-27DOI: 10.1080/22221751.2024.2353298
Yi Xu, Chen Yang, Panpan Sun, Fansen Zeng, Qian Wang, Jianlong Wu, Chunxiao Fang, Che Zhang, Jinping Wang, Yiling Gu, Xiaohuan Wu, Xiaoxian Zhang, Bin Yang, Juhua Yang, Hongwei Zhang, Jiacee Lian, Jinqiu Zhang, Li Huang, Qizhou Lian
With the atypical rise of Mycoplasma pneumoniae infection (MPI) in 2023, prompt studies are needed to determine the current epidemic features and risk factors with emerging trends of MPI to furnish a framework for subsequent investigations. This multicentre, retrospective study was designed to analyse the epidemic patterns of MPI before and after the COVID-19 pandemic, as well as genotypes and the macrolide-resistance-associated mutations in MP sampled from paediatric patients in Southern China. Clinical data was collected from 1,33,674 patients admitted into investigational hospitals from 1 June 2017 to 30 November 2023. Metagenomic next-generation sequencing (mNGS) data were retrieved based on MP sequence positive samples from 299 paediatric patients for macrolide-resistance-associated mutations analysis. Pearson's chi-squared test was used to compare categorical variables between different time frames. The monthly average cases of paediatric common respiratory infection diseases increased without enhanced public health measures after the pandemic, especially for influenza, respiratory syncytial virus infection, and MPI. The contribution of MPI to pneumoniae was similar to that in the outbreak in 2019. Compared to mNGS data between 2019-2022 and 2023, the severity of MP did not grow stronger despite higher rates of macrolide-resistance hypervariable sites, including loci 2063 and 2064, were detected in childhood MP samples of 2023. Our findings indicated that ongoing surveillance is necessary to understand the impact of post pandemic on MP transmission disruption during epidemic season and the severity of clinical outcomes in different scenarios.
{"title":"Epidemic features and megagenomic analysis of childhood <i>Mycoplasma pneumoniae</i> post COVID-19 pandemic: a 6-year study in southern China.","authors":"Yi Xu, Chen Yang, Panpan Sun, Fansen Zeng, Qian Wang, Jianlong Wu, Chunxiao Fang, Che Zhang, Jinping Wang, Yiling Gu, Xiaohuan Wu, Xiaoxian Zhang, Bin Yang, Juhua Yang, Hongwei Zhang, Jiacee Lian, Jinqiu Zhang, Li Huang, Qizhou Lian","doi":"10.1080/22221751.2024.2353298","DOIUrl":"10.1080/22221751.2024.2353298","url":null,"abstract":"<p><p>With the atypical rise of <i>Mycoplasma pneumoniae</i> infection (MPI) in 2023, prompt studies are needed to determine the current epidemic features and risk factors with emerging trends of MPI to furnish a framework for subsequent investigations. This multicentre, retrospective study was designed to analyse the epidemic patterns of MPI before and after the COVID-19 pandemic, as well as genotypes and the macrolide-resistance-associated mutations in <i>MP</i> sampled from paediatric patients in Southern China. Clinical data was collected from 1,33,674 patients admitted into investigational hospitals from 1 June 2017 to 30 November 2023. Metagenomic next-generation sequencing (mNGS) data were retrieved based on <i>MP</i> sequence positive samples from 299 paediatric patients for macrolide-resistance-associated mutations analysis. <i>Pearson's chi-squared test</i> was used to compare categorical variables between different time frames. The monthly average cases of paediatric common respiratory infection diseases increased without enhanced public health measures after the pandemic, especially for influenza, respiratory syncytial virus infection, and MPI. The contribution of MPI to pneumoniae was similar to that in the outbreak in 2019. Compared to mNGS data between 2019-2022 and 2023, the severity of <i>MP</i> did not grow stronger despite higher rates of macrolide-resistance hypervariable sites, including loci 2063 and 2064, were detected in childhood <i>MP</i> samples of 2023. Our findings indicated that ongoing surveillance is necessary to understand the impact of post pandemic on <i>MP</i> transmission disruption during epidemic season and the severity of clinical outcomes in different scenarios.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":null,"pages":null},"PeriodicalIF":8.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11212572/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140891306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01Epub Date: 2024-09-22DOI: 10.1080/22221751.2024.2392667
Shannon L Russell, Cassandra L Andrew, Kevin C Yang, Michelle Coombe, Glenna McGregor, Tony Redford, Agatha N Jassem, James E A Zlosnik, Jolene Giacinti, Kevin S Kuchinski, John L Palmer, John R Tyson, Chris Fjell, Megan Willie, Megan V Ross, Maeve Winchester, Laurie Wilson, Yohannes Berhane, Caeley Thacker, N Jane Harms, Catherine Soos, Theresa Burns, Natalie Prystajecky, Chelsea Himsworth
Surveillance data from wildlife and poultry was used to describe the spread of highly pathogenic avian influenza (HPAI) H5N1 clade 2.3.4.4b in British Columbia (B.C.) and the Yukon, Canada from September 2022 - June 2023 compared to the first "wave" of the outbreak in this region, which occurred April - August 2022, after the initial viral introduction. Although the number of HPAI-positive poultry farms and wildlife samples was greater in "Wave 2", cases were more tightly clustered in southwestern B.C. and the most commonly affected species differed, likely due to an influx of overwintering waterfowl in the area. Eight HPAI genetic clusters, representing seven genotypes and two inter-continental viral incursions, were detected, with significant variation in the relative abundance of each cluster between the waves. Phylogenetic data suggests multiple spillover events from wild birds to poultry and mammals but could not rule out transmission among farms and among mammals.
{"title":"Descriptive epidemiology and phylogenetic analysis of highly pathogenic avian influenza H5N1 clade 2.3.4.4b in British Columbia (B.C.) and the Yukon, Canada, September 2022 to June 2023.","authors":"Shannon L Russell, Cassandra L Andrew, Kevin C Yang, Michelle Coombe, Glenna McGregor, Tony Redford, Agatha N Jassem, James E A Zlosnik, Jolene Giacinti, Kevin S Kuchinski, John L Palmer, John R Tyson, Chris Fjell, Megan Willie, Megan V Ross, Maeve Winchester, Laurie Wilson, Yohannes Berhane, Caeley Thacker, N Jane Harms, Catherine Soos, Theresa Burns, Natalie Prystajecky, Chelsea Himsworth","doi":"10.1080/22221751.2024.2392667","DOIUrl":"10.1080/22221751.2024.2392667","url":null,"abstract":"<p><p>Surveillance data from wildlife and poultry was used to describe the spread of highly pathogenic avian influenza (HPAI) H5N1 clade 2.3.4.4b in British Columbia (B.C.) and the Yukon, Canada from September 2022 - June 2023 compared to the first \"wave\" of the outbreak in this region, which occurred April - August 2022, after the initial viral introduction. Although the number of HPAI-positive poultry farms and wildlife samples was greater in \"Wave 2\", cases were more tightly clustered in southwestern B.C. and the most commonly affected species differed, likely due to an influx of overwintering waterfowl in the area. Eight HPAI genetic clusters, representing seven genotypes and two inter-continental viral incursions, were detected, with significant variation in the relative abundance of each cluster between the waves. Phylogenetic data suggests multiple spillover events from wild birds to poultry and mammals but could not rule out transmission among farms and among mammals.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":null,"pages":null},"PeriodicalIF":8.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11421163/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141981977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01Epub Date: 2024-10-13DOI: 10.1080/22221751.2024.2412624
Jahid Hasan Tipu, Audun Sivertsen, Jan-Egil Afset, Lars Sandven, Hanne Brekke, Hilde Marie Lund, Linnea Sofie Elburg, Peter Gaustad, Tore Lier, Liv Reidun Tverelv, Øystein Haarklau Johansen, Lucy J Robertson, Kurt Hanevik
PCR-based diagnostics has revealed the previously largely unknown Cryptosporidium transmission and infections in high-income countries. This study aimed to determine domestic and imported subtypes of Cryptosporidium species in Norway, evaluate their demographic distribution, and identify potential small outbreaks. Cryptosporidium-positive human faecal samples were obtained from six medical microbiology laboratories between February 2022 and January 2024, together with 22 Cryptosporidium-positive animal samples. Species and subtypes were identified by sequencing PCR products from gp60 and SSU rRNA genes. Most cryptosporidiosis cases occurred during late summer/early autumn, primarily in children and young adults. Of 550 human samples, 359 were successfully characterized molecularly (65%), revealing infection with 10 different Cryptosporidium species. C. parvum occurred in 245 (68%) human isolates with IIa and IId being major allele families, with distinct regional distribution patterns of common subtypes. A kindergarten outbreak with 5 cases was due to C. parvum IIaA14G1R1. C. mortiferum was identified in 33 (9.2%) human cases of which 24 were known to be of domestic origin, making it the second most common species in human autochthonous cases in Norway. All C. mortiferum isolates were of the same genotype; XIVaA20G2T1, including 13 cases from a suspected small outbreak in Trøndelag. C. hominis occurred in 68 typed cases (19%), but mostly in infections acquired abroad, with allele families Ib and If occurring most often. In conclusion, this study of recent Cryptosporidium spp. and subtypes in Norway, highlights the predominance of C. parvum and the emergence of C. mortiferum among autochthonous cases.
{"title":"<i>Cryptosporidium</i> species and subtypes in Norway: predominance of <i>C. parvum</i> and emergence of <i>C. mortiferum</i>.","authors":"Jahid Hasan Tipu, Audun Sivertsen, Jan-Egil Afset, Lars Sandven, Hanne Brekke, Hilde Marie Lund, Linnea Sofie Elburg, Peter Gaustad, Tore Lier, Liv Reidun Tverelv, Øystein Haarklau Johansen, Lucy J Robertson, Kurt Hanevik","doi":"10.1080/22221751.2024.2412624","DOIUrl":"10.1080/22221751.2024.2412624","url":null,"abstract":"<p><p>PCR-based diagnostics has revealed the previously largely unknown <i>Cryptosporidium</i> transmission and infections in high-income countries. This study aimed to determine domestic and imported subtypes of <i>Cryptosporidium</i> species in Norway, evaluate their demographic distribution, and identify potential small outbreaks. <i>Cryptosporidium</i>-positive human faecal samples were obtained from six medical microbiology laboratories between February 2022 and January 2024, together with 22 <i>Cryptosporidium</i>-positive animal samples. Species and subtypes were identified by sequencing PCR products from gp60 and SSU rRNA genes. Most cryptosporidiosis cases occurred during late summer/early autumn, primarily in children and young adults. Of 550 human samples, 359 were successfully characterized molecularly (65%), revealing infection with 10 different <i>Cryptosporidium</i> species. <i>C. parvum</i> occurred in 245 (68%) human isolates with IIa and IId being major allele families, with distinct regional distribution patterns of common subtypes. A kindergarten outbreak with 5 cases was due to <i>C. parvum</i> IIaA14G1R1. <i>C. mortiferum</i> was identified in 33 (9.2%) human cases of which 24 were known to be of domestic origin, making it the second most common species in human autochthonous cases in Norway. All <i>C. mortiferum</i> isolates were of the same genotype; XIVaA20G2T1, including 13 cases from a suspected small outbreak in Trøndelag. <i>C. hominis</i> occurred in 68 typed cases (19%), but mostly in infections acquired abroad, with allele families Ib and If occurring most often. In conclusion, this study of recent <i>Cryptosporidium</i> spp. and subtypes in Norway, highlights the predominance of <i>C. parvum</i> and the emergence of <i>C. mortiferum</i> among autochthonous cases.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":null,"pages":null},"PeriodicalIF":8.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11485689/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Epstein-Barr virus (EBV) infection has been related to multiple epithelial cancers and lymphomas. Current efforts in developing a prophylactic EBV vaccine have focused on inducing neutralizing antibodies. However, given the lifelong and persistent nature of EBV infection following primary infection, it is rationalized that an ideal vaccine should elicit both humoral and cellular immune responses targeting multiple stages of the EBV lifecycle. This study used a DNA vector and a TianTan vaccinia virus to express key EBV antigens, including BZLF1, EBNA1, EBNA3B, and gH/gL, to generate multi-antigen vaccines. The multi-antigen vaccine expressing all four antigens and the multi-antigen vaccine expressing BZLF1, EBNA1, and EBNA3B showed comparable protection effects and prevented 100% and 80% of humanized mice, respectively, from EBV-induced fatal B cell lymphoma by activating BZLF1, EBNA1, and EBNA3B specific T cell. The vaccine expressing lytic protein BZLF1 elicited stronger T cell responses and conferred superior protection compared to vaccines targeting single latent EBNA1 or EBNA3B. The vaccine solely expressing gH/gL exhibited no T cell protective effects in our humanized mice model. Our study implicates the potential of EBV vaccines that induce potent cellular responses targeting both latent and lytic phases of the EBV life cycle in the prevention of EBV-induced B cell lymphoma.
摘要天疱疮病毒(EBV)感染与多种上皮癌和淋巴瘤有关。目前,开发预防性 EBV 疫苗的工作主要集中在诱导中和抗体上。然而,鉴于 EBV 感染在原发感染后会终身持续存在,因此理想的疫苗应该针对 EBV 生命周期的多个阶段引起体液免疫和细胞免疫反应。本研究使用 DNA 载体和天坛疫苗病毒表达 EBV 的关键抗原,包括 BZLF1、EBNA1、EBNA3B 和 gH/gL,以产生多抗原疫苗。通过激活 BZLF1、EBNA1 和 EBNA3B 特异性 T 细胞,表达所有四种抗原的多抗原疫苗和表达 BZLF1、EBNA1 和 EBNA3B 的多抗原疫苗显示出了相当的保护效果,分别 100% 和 80% 的人源化小鼠免于 EBV 诱导的致命 B 细胞淋巴瘤。与针对单一潜伏 EBNA1 或 EBNA3B 的疫苗相比,表达溶菌蛋白 BZLF1 的疫苗能激发更强的 T 细胞反应,并提供更优越的保护。在我们的人源化小鼠模型中,仅表达 gH/gL 的疫苗没有表现出 T 细胞保护作用。我们的研究表明,针对 EBV 生命周期的潜伏期和溶解期诱导强效细胞应答的 EBV 疫苗具有预防 EBV 诱导的 B 细胞淋巴瘤的潜力。
{"title":"TianTan vaccinia virus-based EBV vaccines targeting both latent and lytic antigens elicits potent immunity against lethal EBV challenge in humanized mice.","authors":"Xinyu Zhang, Yanhong Chen, Shuhui Wang, Ling Zhong, Zheng Xiang, Xiao Zhang, Shanshan Zhang, Xiang Zhou, Wanlin Zhang, Yan Zhou, Qiuting Zhang, Jingtong Liang, Yanran Luo, Yufei Wang, Ling Chen, Xiaoping Ye, Qisheng Feng, Mu-Sheng Zeng, Ying Liu, Yi-Xin Zeng, Yiming Shao, Miao Xu","doi":"10.1080/22221751.2024.2412640","DOIUrl":"10.1080/22221751.2024.2412640","url":null,"abstract":"<p><p>Epstein-Barr virus (EBV) infection has been related to multiple epithelial cancers and lymphomas. Current efforts in developing a prophylactic EBV vaccine have focused on inducing neutralizing antibodies. However, given the lifelong and persistent nature of EBV infection following primary infection, it is rationalized that an ideal vaccine should elicit both humoral and cellular immune responses targeting multiple stages of the EBV lifecycle. This study used a DNA vector and a TianTan vaccinia virus to express key EBV antigens, including BZLF1, EBNA1, EBNA3B, and gH/gL, to generate multi-antigen vaccines. The multi-antigen vaccine expressing all four antigens and the multi-antigen vaccine expressing BZLF1, EBNA1, and EBNA3B showed comparable protection effects and prevented 100% and 80% of humanized mice, respectively, from EBV-induced fatal B cell lymphoma by activating BZLF1, EBNA1, and EBNA3B specific T cell. The vaccine expressing lytic protein BZLF1 elicited stronger T cell responses and conferred superior protection compared to vaccines targeting single latent EBNA1 or EBNA3B. The vaccine solely expressing gH/gL exhibited no T cell protective effects in our humanized mice model. Our study implicates the potential of EBV vaccines that induce potent cellular responses targeting both latent and lytic phases of the EBV life cycle in the prevention of EBV-induced B cell lymphoma.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":null,"pages":null},"PeriodicalIF":8.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11485817/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01Epub Date: 2024-06-05DOI: 10.1080/22221751.2024.2361814
Liu Ying, Sun Qiang, Xiao Jinbo, Ren Binzhi, Zhao Hua, Shi Yong, Zhou Shuaifeng, Hong Mei, Zhou Kangping, Cun Jianping, Zeng Yunting, Chen Jianhua, Ge Qiong, Ju Yu, Lu Huanhuan, Li Jichen, Cong Ruyi, Yang Tingting, Wang Rui, Zong Yanjun, Sun Tiantian, Yu Liheng, Wang Xiaoyi, Zhu Shuangli, Yan Dongmei, Ji Tianjiao, Yang Qian, Zhu Zhen, Zhang Yong
Echovirus 11 (E11) has gained attention owing to its association with severe neonatal infections. From 2018 to 2023, a surge in severe neonatal cases and fatalities linked to a novel variant of genotype D5 was documented in China, France, and Italy. However, the prevention and control of E11 variants have been hampered by limited background data on the virus circulation and genetic variance. Therefore, the present study investigated the circulating dynamics of E11 and the genetic variation and molecular evolution of genotype D5 through the collection of strains from the national acute flaccid paralysis (AFP) and hand, foot, and mouth disease (HFMD) surveillance system in China during 2000-2022 and genetic sequences published in the GenBank database. The results of this study revealed a prevalent dynamic of E11 circulation, with D5 being the predominant genotype worldwide. Further phylogenetic analysis of genotype D5 indicated that it could be subdivided into three important geographic clusters (D5-CHN1: 2014-2019, D5-CHN2: 2016-2022, and D5-EUR: 2022-2023). Additionally, variant-specific (144) amino acid mutation sites and positive-selection pressure sites (132, 262) were identified in the VP1 region. Cluster-specific recombination patterns were also identified, with CVB5, E6, and CVB4 as the major recombinant viruses. These findings provide a preliminary landscape of E11 circulation worldwide and basic scientific data for further study of the pathogenicity of E11 variants.
{"title":"Genetic variation and evolutionary characteristics of Echovirus 11: new variant within genotype D5 associated with neonatal death found in China.","authors":"Liu Ying, Sun Qiang, Xiao Jinbo, Ren Binzhi, Zhao Hua, Shi Yong, Zhou Shuaifeng, Hong Mei, Zhou Kangping, Cun Jianping, Zeng Yunting, Chen Jianhua, Ge Qiong, Ju Yu, Lu Huanhuan, Li Jichen, Cong Ruyi, Yang Tingting, Wang Rui, Zong Yanjun, Sun Tiantian, Yu Liheng, Wang Xiaoyi, Zhu Shuangli, Yan Dongmei, Ji Tianjiao, Yang Qian, Zhu Zhen, Zhang Yong","doi":"10.1080/22221751.2024.2361814","DOIUrl":"10.1080/22221751.2024.2361814","url":null,"abstract":"<p><p>Echovirus 11 (E11) has gained attention owing to its association with severe neonatal infections. From 2018 to 2023, a surge in severe neonatal cases and fatalities linked to a novel variant of genotype D5 was documented in China, France, and Italy. However, the prevention and control of E11 variants have been hampered by limited background data on the virus circulation and genetic variance. Therefore, the present study investigated the circulating dynamics of E11 and the genetic variation and molecular evolution of genotype D5 through the collection of strains from the national acute flaccid paralysis (AFP) and hand, foot, and mouth disease (HFMD) surveillance system in China during 2000-2022 and genetic sequences published in the GenBank database. The results of this study revealed a prevalent dynamic of E11 circulation, with D5 being the predominant genotype worldwide. Further phylogenetic analysis of genotype D5 indicated that it could be subdivided into three important geographic clusters (D5-CHN1: 2014-2019, D5-CHN2: 2016-2022, and D5-EUR: 2022-2023). Additionally, variant-specific (144) amino acid mutation sites and positive-selection pressure sites (132, 262) were identified in the <i>VP1</i> region. Cluster-specific recombination patterns were also identified, with CVB5, E6, and CVB4 as the major recombinant viruses. These findings provide a preliminary landscape of E11 circulation worldwide and basic scientific data for further study of the pathogenicity of E11 variants.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":null,"pages":null},"PeriodicalIF":8.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11159588/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141199661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01Epub Date: 2024-04-17DOI: 10.1080/22221751.2023.2297552
Jurre Y Siegers, Michelle Wille, Sokhoun Yann, Songha Tok, Sarath Sin, Sokha Chea, Alice Porco, Sreyem Sours, Vutha Chim, Samban Chea, Kimtuo Chhel, Sothyra Tum, San Sorn, Makara Hak, Peter Thielen, Vijaykrishna Dhanasekaran, Erik A Karlsson
Avian influenza virus (AIV) in Asia is a complex system with numerous subtypes and a highly porous wild birds-poultry interface. Certain AIV subtypes, such as H14, are underrepresented in current surveillance efforts, leaving gaps in our understanding of their ecology and evolution. The detection of rare subtype H14 in domestic ducks in Southeast Asia comprises a geographic region and domestic bird population previously unassociated with this subtype. These H14 viruses have a complex evolutionary history involving gene reassortment events. They share sequence similarity to AIVs endemic in Cambodian ducks, and Eurasian low pathogenicity and high pathogenicity H5Nx AIVs. The detection of these H14 viruses in Southeast Asian domestic poultry further advances our knowledge of the ecology and evolution of this subtype and reinforces the need for continued, longitudinal, active surveillance in domestic and wild birds. Additionally, in vivo and in vitro risk assessment should encompass rare AIV subtypes, as they have the potential to establish in poultry systems.
{"title":"Detection and phylogenetic analysis of contemporary H14N2 Avian influenza A virus in domestic ducks in Southeast Asia (Cambodia).","authors":"Jurre Y Siegers, Michelle Wille, Sokhoun Yann, Songha Tok, Sarath Sin, Sokha Chea, Alice Porco, Sreyem Sours, Vutha Chim, Samban Chea, Kimtuo Chhel, Sothyra Tum, San Sorn, Makara Hak, Peter Thielen, Vijaykrishna Dhanasekaran, Erik A Karlsson","doi":"10.1080/22221751.2023.2297552","DOIUrl":"10.1080/22221751.2023.2297552","url":null,"abstract":"<p><p>Avian influenza virus (AIV) in Asia is a complex system with numerous subtypes and a highly porous wild birds-poultry interface. Certain AIV subtypes, such as H14, are underrepresented in current surveillance efforts, leaving gaps in our understanding of their ecology and evolution. The detection of rare subtype H14 in domestic ducks in Southeast Asia comprises a geographic region and domestic bird population previously unassociated with this subtype. These H14 viruses have a complex evolutionary history involving gene reassortment events. They share sequence similarity to AIVs endemic in Cambodian ducks, and Eurasian low pathogenicity and high pathogenicity H5Nx AIVs. The detection of these H14 viruses in Southeast Asian domestic poultry further advances our knowledge of the ecology and evolution of this subtype and reinforces the need for continued, longitudinal, active surveillance in domestic and wild birds. Additionally, <i>in vivo</i> and <i>in vitro</i> risk assessment should encompass rare AIV subtypes, as they have the potential to establish in poultry systems.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":null,"pages":null},"PeriodicalIF":13.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11025406/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138795446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01Epub Date: 2024-08-08DOI: 10.1080/22221751.2024.2387906
Laura Marcos-Villar, Beatriz Perdiguero, María López-Bravo, Carmen Zamora, Laura Sin, Enrique Álvarez, Carlos Óscar S Sorzano, Pedro J Sánchez-Cordón, José M Casasnovas, David Astorgano, Juan García-Arriaza, Shubaash Anthiya, Mireya L Borrajo, Gustavo Lou, Belén Cuesta, Lorenzo Franceschini, Josep L Gelpí, Kris Thielemans, Marta Sisteré-Oró, Andreas Meyerhans, Felipe García, Ignasi Esteban, Núria López-Bigas, Montserrat Plana, María J Alonso, Mariano Esteban, Carmen Elena Gómez
Despite the high efficiency of current SARS-CoV-2 mRNA vaccines in reducing COVID-19 morbidity and mortality, waning immunity and the emergence of resistant variants underscore the need for novel vaccination strategies. This study explores a heterologous mRNA/Modified Vaccinia virus Ankara (MVA) prime/boost regimen employing a trimeric form of the receptor binding domain (RBD) of the SARS-CoV-2 spike (S) protein compared to a homologous MVA/MVA regimen. In C57BL/6 mice, the RBD was delivered during priming via an mRNA vector encapsulated in nanoemulsions (NE) or lipid nanoparticles (LNP), followed by a booster with a replication-deficient MVA-based recombinant virus (MVA-RBD). This heterologous mRNA/MVA regimen elicited strong anti-RBD binding and neutralizing antibodies (BAbs and NAbs) against both the ancestral SARS-CoV-2 strain and different variants of concern (VoCs). Additionally, this protocol induced robust and polyfunctional RBD-specific CD4 and CD8 T cell responses, particularly in animals primed with mLNP-RBD. In K18-hACE2 transgenic mice, the LNP-RBD/MVA combination provided complete protection from morbidity and mortality following a live SARS-CoV-2 challenge compared with the partial protection observed with mNE-RBD/MVA or MVA/MVA regimens. Although the mNE-RBD/MVA regimen only protects half of the animals, it was able to induce antibodies with Fc-mediated effector functions besides NAbs. Moreover, viral replication and viral load in the respiratory tract were markedly reduced and decreased pro-inflammatory cytokine levels were observed. These results support the efficacy of heterologous mRNA/MVA vaccine combinations over homologous MVA/MVA regimen, using alternative nanocarriers that circumvent intellectual property restrictions of current mRNA vaccine formulations.
{"title":"Heterologous mRNA/MVA delivering trimeric-RBD as effective vaccination regimen against SARS-CoV-2: COVARNA Consortium.","authors":"Laura Marcos-Villar, Beatriz Perdiguero, María López-Bravo, Carmen Zamora, Laura Sin, Enrique Álvarez, Carlos Óscar S Sorzano, Pedro J Sánchez-Cordón, José M Casasnovas, David Astorgano, Juan García-Arriaza, Shubaash Anthiya, Mireya L Borrajo, Gustavo Lou, Belén Cuesta, Lorenzo Franceschini, Josep L Gelpí, Kris Thielemans, Marta Sisteré-Oró, Andreas Meyerhans, Felipe García, Ignasi Esteban, Núria López-Bigas, Montserrat Plana, María J Alonso, Mariano Esteban, Carmen Elena Gómez","doi":"10.1080/22221751.2024.2387906","DOIUrl":"10.1080/22221751.2024.2387906","url":null,"abstract":"<p><p>Despite the high efficiency of current SARS-CoV-2 mRNA vaccines in reducing COVID-19 morbidity and mortality, waning immunity and the emergence of resistant variants underscore the need for novel vaccination strategies. This study explores a heterologous mRNA/Modified Vaccinia virus Ankara (MVA) prime/boost regimen employing a trimeric form of the receptor binding domain (RBD) of the SARS-CoV-2 spike (S) protein compared to a homologous MVA/MVA regimen. In C57BL/6 mice, the RBD was delivered during priming via an mRNA vector encapsulated in nanoemulsions (NE) or lipid nanoparticles (LNP), followed by a booster with a replication-deficient MVA-based recombinant virus (MVA-RBD). This heterologous mRNA/MVA regimen elicited strong anti-RBD binding and neutralizing antibodies (BAbs and NAbs) against both the ancestral SARS-CoV-2 strain and different variants of concern (VoCs). Additionally, this protocol induced robust and polyfunctional RBD-specific CD4 and CD8 T cell responses, particularly in animals primed with mLNP-RBD. In K18-hACE2 transgenic mice, the LNP-RBD/MVA combination provided complete protection from morbidity and mortality following a live SARS-CoV-2 challenge compared with the partial protection observed with mNE-RBD/MVA or MVA/MVA regimens. Although the mNE-RBD/MVA regimen only protects half of the animals, it was able to induce antibodies with Fc-mediated effector functions besides NAbs. Moreover, viral replication and viral load in the respiratory tract were markedly reduced and decreased pro-inflammatory cytokine levels were observed. These results support the efficacy of heterologous mRNA/MVA vaccine combinations over homologous MVA/MVA regimen, using alternative nanocarriers that circumvent intellectual property restrictions of current mRNA vaccine formulations.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":null,"pages":null},"PeriodicalIF":8.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11313003/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141859284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}