Pub Date : 2024-12-01Epub Date: 2024-05-26DOI: 10.1080/22221751.2024.2356140
Maxime Cochin, Jean-Sélim Driouich, Grégory Moureau, Géraldine Piorkowski, Xavier de Lamballerie, Antoine Nougairède
Reverse genetic systems are mainly used to rescue recombinant viral strains in cell culture. These tools have also been used to generate, by inoculating infectious clones, viral strains directly in living animals. We previously developed the "Infectious Subgenomic Amplicons" (ISA) method, which enables the rescue of single-stranded positive sense RNA viruses in vitro by transfecting overlapping subgenomic DNA fragments. Here, we provide proof-of-concept for direct in vivo generation of infectious particles following the inoculation of subgenomic amplicons. First, we rescued a strain of tick-borne encephalitis virus in mice to transpose the ISA method in vivo. Subgenomic DNA fragments were amplified using a 3-fragment reverse genetics system and inoculated intramuscularly. Almost all animals were infected when quantities of DNA inoculated were at least 20 µg. We then optimized our procedure in order to increase the animal infection rate. This was achieved by adding an electroporation step and/or using a simplified 2- fragment reverse genetics system. Under optimal conditions, a large majority of animals were infected with doses of 20 ng of DNA. Finally, we demonstrated the versatility of this method by applying it to Japanese encephalitis and Chikungunya viruses. This method provides an efficient strategy for in vivo rescue of arboviruses. Furthermore, in the context of the development of DNA-launched live attenuated vaccines, this new approach may facilitate the generation of attenuated strains in vivo. It also enables to deliver a substance free of any vector DNA, which seems to be an important criterion for the development of human vaccines.
反向遗传系统主要用于挽救细胞培养中的重组病毒株。我们之前开发了 "感染性亚基因组扩增子"(ISA)方法,通过转染重叠的亚基因组 DNA 片段在体外挽救单链正义 RNA 病毒。在这里,我们提供了接种亚基因组扩增子后在体内直接产生感染性颗粒的概念验证。首先,我们在小鼠体内拯救了一株蜱传脑炎病毒,在体内转染 ISA 方法。使用 3 片段反向遗传学系统扩增亚基因组 DNA 片段,并将其肌肉注射到动物体内。当接种的 DNA 数量至少为 20µg 时,几乎所有动物都受到了感染。随后,我们对程序进行了优化,以提高动物感染率。为此,我们增加了电穿孔步骤和/或使用简化的 2 片段反向遗传系统。在最佳条件下,绝大多数动物的 DNA 感染剂量为 20ng。最后,我们将这种方法应用于日本脑炎和基孔肯雅病毒,证明了它的多功能性。此外,在开发 DNA 发射减毒活疫苗的背景下,这种新方法可促进体内减毒株的产生。它还能提供不含任何载体 DNA 的物质,这似乎是开发人类疫苗的一个重要标准。
{"title":"<i>In vivo</i> rescue of arboviruses directly from subgenomic DNA fragments.","authors":"Maxime Cochin, Jean-Sélim Driouich, Grégory Moureau, Géraldine Piorkowski, Xavier de Lamballerie, Antoine Nougairède","doi":"10.1080/22221751.2024.2356140","DOIUrl":"10.1080/22221751.2024.2356140","url":null,"abstract":"<p><p>Reverse genetic systems are mainly used to rescue recombinant viral strains in cell culture. These tools have also been used to generate, by inoculating infectious clones, viral strains directly in living animals. We previously developed the \"Infectious Subgenomic Amplicons\" (ISA) method, which enables the rescue of single-stranded positive sense RNA viruses <i>in vitro</i> by transfecting overlapping subgenomic DNA fragments. Here, we provide proof-of-concept for direct <i>in vivo</i> generation of infectious particles following the inoculation of subgenomic amplicons. First, we rescued a strain of tick-borne encephalitis virus in mice to transpose the ISA method <i>in vivo</i>. Subgenomic DNA fragments were amplified using a 3-fragment reverse genetics system and inoculated intramuscularly. Almost all animals were infected when quantities of DNA inoculated were at least 20 µg. We then optimized our procedure in order to increase the animal infection rate. This was achieved by adding an electroporation step and/or using a simplified 2- fragment reverse genetics system. Under optimal conditions, a large majority of animals were infected with doses of 20 ng of DNA. Finally, we demonstrated the versatility of this method by applying it to Japanese encephalitis and Chikungunya viruses. This method provides an efficient strategy for <i>in vivo</i> rescue of arboviruses. Furthermore, in the context of the development of DNA-launched live attenuated vaccines, this new approach may facilitate the generation of attenuated strains <i>in vivo</i>. It also enables to deliver a substance free of any vector DNA, which seems to be an important criterion for the development of human vaccines.</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/PMC11133884/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140916273","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: 2024-03-03DOI: 10.1080/22221751.2024.2322649
Ehab A Salama, Yehia Elgammal, Aruna Wijeratne, Nadia A Lanman, Sagar M Utturkar, Atena Farhangian, Jianing Li, Brigitte Meunier, Tony R Hazbun, Mohamed N Seleem
Candida auris has emerged as a problematic fungal pathogen associated with high morbidity and mortality. Amphotericin B (AmB) is the most effective antifungal used to treat invasive fungal candidiasis, with resistance rarely observed among clinical isolates. However, C. auris possesses extraordinary resistant profiles against all available antifungal drugs, including AmB. In our pursuit of potential solutions, we screened a panel of 727 FDA-approved drugs. We identified the proton pump inhibitor lansoprazole (LNP) as a potent enhancer of AmB's activity against C. auris. LNP also potentiates the antifungal activity of AmB against other medically important species of Candida and Cryptococcus. Our investigations into the mechanism of action unveiled that LNP metabolite(s) interact with a crucial target in the mitochondrial respiratory chain (complex III, known as cytochrome bc1). This interaction increases oxidative stress within fungal cells. Our results demonstrated the critical role of an active respiratory function in the antifungal activity of LNP. Most importantly, LNP restored the efficacy of AmB in an immunocompromised mouse model, resulting in a 1.7-log (∼98%) CFU reduction in the burden of C. auris in the kidneys. Our findings strongly advocate for a comprehensive evaluation of LNP as a cytochrome bc1 inhibitor for combating drug-resistant C. auris infections.
白色念珠菌已成为一种棘手的真菌病原体,发病率和死亡率都很高。两性霉素 B(AmB)是治疗侵袭性真菌念珠菌病最有效的抗真菌药物,临床分离株很少出现耐药性。然而,念珠菌对包括两性霉素 B 在内的所有现有抗真菌药物都具有极强的耐药性。为了寻求潜在的解决方案,我们筛选了 727 种美国食品及药物管理局批准的药物。我们发现质子泵抑制剂兰索拉唑(LNP)能有效增强 AmB 对阿氏杆菌的活性。LNP 还能增强 AmB 对其他重要医学念珠菌和隐球菌的抗真菌活性。我们对其作用机制的研究发现,LNP 代谢物与线粒体呼吸链(复合体 III,即细胞色素 bc1)中的一个关键靶点相互作用。这种相互作用增加了真菌细胞内的氧化应激。我们的研究结果表明,活跃的呼吸功能在 LNP 的抗真菌活性中起着关键作用。最重要的是,LNP 恢复了 AmB 在免疫功能低下小鼠模型中的疗效,使肾脏中的阴沟肠杆菌负担减少了 1.7 个菌落(∼98%)。我们的研究结果强烈建议将 LNP 作为细胞色素 bc1 抑制剂进行全面评估,以抗击耐药性蛔虫感染。
{"title":"Lansoprazole interferes with fungal respiration and acts synergistically with amphotericin B against multidrug-resistant <i>Candida auris</i>.","authors":"Ehab A Salama, Yehia Elgammal, Aruna Wijeratne, Nadia A Lanman, Sagar M Utturkar, Atena Farhangian, Jianing Li, Brigitte Meunier, Tony R Hazbun, Mohamed N Seleem","doi":"10.1080/22221751.2024.2322649","DOIUrl":"10.1080/22221751.2024.2322649","url":null,"abstract":"<p><p><i>Candida auris</i> has emerged as a problematic fungal pathogen associated with high morbidity and mortality. Amphotericin B (AmB) is the most effective antifungal used to treat invasive fungal candidiasis, with resistance rarely observed among clinical isolates. However, <i>C. auris</i> possesses extraordinary resistant profiles against all available antifungal drugs, including AmB. In our pursuit of potential solutions, we screened a panel of 727 FDA-approved drugs. We identified the proton pump inhibitor lansoprazole (LNP) as a potent enhancer of AmB's activity against <i>C. auris.</i> LNP also potentiates the antifungal activity of AmB against other medically important species of <i>Candida</i> and <i>Cryptococcus.</i> Our investigations into the mechanism of action unveiled that LNP metabolite(s) interact with a crucial target in the mitochondrial respiratory chain (complex III, known as cytochrome <i>bc<sub>1</sub></i>). This interaction increases oxidative stress within fungal cells. Our results demonstrated the critical role of an active respiratory function in the antifungal activity of LNP. Most importantly, LNP restored the efficacy of AmB in an immunocompromised mouse model, resulting in a 1.7-log (∼98%) CFU reduction in the burden of <i>C. auris</i> in the kidneys. Our findings strongly advocate for a comprehensive evaluation of LNP as a cytochrome <i>bc<sub>1</sub></i> inhibitor for combating drug-resistant <i>C. auris</i> infections.</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/PMC10911247/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140021221","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: 2024-05-15DOI: 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: 2024-04-17DOI: 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}
Pub Date : 2024-12-01Epub Date: 2024-08-16DOI: 10.1080/22221751.2024.2387442
Hao Liu, Wenjing Wang, Yang Zhang, Fuchun Wang, Junyi Duan, Tao Huang, Xiaojie Huang, Tong Zhang
A large outbreak of monkeypox occurred in 2022, and most people lack immunity to orthopoxvirus. Smallpox vaccination is essential for preventing further smallpox outbreaks. This study evaluated the effectiveness, protection, safety, and cross-immunogenicity of smallpox vaccine in preventing monkeypox infection. PubMed, Embase, Scopus, and Web of Science were searched from database inception to 10 March 2024. We included studies involving "monkeypox virus" and "vaccinations", and excluded reviews, animal studies, and articles with missing or duplicate data. A total of 37 studies with 57,693 participants were included in the final analysis. The effectiveness data showed that monkeypox infection rates were lower in the smallpox-vaccinated group than in the unvaccinated group (risk ratio [RR]: 0.46; 95% confidence interval [CI]: 0.31-0.68). The protection data showed that smallpox vaccination effectively reduced the risk of severe monkeypox infection (RR: 0.61; 95% CI: 0.42-0.87). Third-generation vaccines showed greater efficacy (RR: 0.36, 95% CI: 0.22-0.56) than first-generation vaccines. The number of doses of smallpox vaccine has no significant effect on monkeypox. Safety data showed that adverse reactions after smallpox vaccination were mainly mild and included local erythema, swelling, induration, itching, and pain. Meanwhile, we found that smallpox vaccination could induce the production of neutralizing antibodies against monkeypox. Our findings offer compelling evidence supporting the clinical application of the smallpox vaccine for preventing monkeypox and advocate that high-risk groups should be prioritized for receiving one dose of the smallpox vaccine if the vaccine stockpile is low.
{"title":"Global perspectives on smallpox vaccine against monkeypox: a comprehensive meta-analysis and systematic review of effectiveness, protection, safety and cross-immunogenicity.","authors":"Hao Liu, Wenjing Wang, Yang Zhang, Fuchun Wang, Junyi Duan, Tao Huang, Xiaojie Huang, Tong Zhang","doi":"10.1080/22221751.2024.2387442","DOIUrl":"10.1080/22221751.2024.2387442","url":null,"abstract":"<p><p>A large outbreak of monkeypox occurred in 2022, and most people lack immunity to orthopoxvirus. Smallpox vaccination is essential for preventing further smallpox outbreaks. This study evaluated the effectiveness, protection, safety, and cross-immunogenicity of smallpox vaccine in preventing monkeypox infection. PubMed, Embase, Scopus, and Web of Science were searched from database inception to 10 March 2024. We included studies involving \"monkeypox virus\" and \"vaccinations\", and excluded reviews, animal studies, and articles with missing or duplicate data. A total of 37 studies with 57,693 participants were included in the final analysis. The effectiveness data showed that monkeypox infection rates were lower in the smallpox-vaccinated group than in the unvaccinated group (risk ratio [RR]: 0.46; 95% confidence interval [CI]: 0.31-0.68). The protection data showed that smallpox vaccination effectively reduced the risk of severe monkeypox infection (RR: 0.61; 95% CI: 0.42-0.87). Third-generation vaccines showed greater efficacy (RR: 0.36, 95% CI: 0.22-0.56) than first-generation vaccines. The number of doses of smallpox vaccine has no significant effect on monkeypox. Safety data showed that adverse reactions after smallpox vaccination were mainly mild and included local erythema, swelling, induration, itching, and pain. Meanwhile, we found that smallpox vaccination could induce the production of neutralizing antibodies against monkeypox. Our findings offer compelling evidence supporting the clinical application of the smallpox vaccine for preventing monkeypox and advocate that high-risk groups should be prioritized for receiving one dose of the smallpox vaccine if the vaccine stockpile is low.</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/PMC11332295/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141855205","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: 2024-01-30DOI: 10.1080/22221751.2023.2290842
Yakhouba Kane, Alexander Tendu, Ruiya Li, Yanhua Chen, Emilio Mastriani, Jiaming Lan, Alice Catherine Hughes, Nicolas Berthet, Gary Wong
Rodents represent over 40% of known mammal species and are found in various terrestrial habitats. They are significant reservoirs for zoonotic viruses, including harmful pathogens such as arenaviruses and hantaviruses, yet knowledge of their hosts and distributions is limited. Therefore, characterizing the virome profile in these animals is invaluable for outbreak preparedness, especially in potential hotspots of mammal diversity. This study included 681 organs from 124 rodents and one Chinese tree shrew collected from Yunnan Province, China, during 2020-2021. Metagenomic analysis revealed unique features of mammalian viruses in rodent organs across habitats with varying human disturbances. R. tanezumi in locations with high anthropogenic disturbance exhibited the highest mammal viral diversity, with spleen and lung samples showing the highest diversities for these viruses at the organ level. Mammal viral diversity for both commensal and non-commensal rats was identified to positively correlate with landscape disturbance. Some virus families were associated with particular organs or host species, suggesting tropism for these pathogens. Notably, known and novel viral species that are likely to infect humans were identified. R. tanezumi was identified as a reservoir and carrier for various zoonotic viruses, including porcine bocavirus, hantavirus, cardiovirus, and lyssavirus. These findings highlight the influence of rodent community composition and anthropogenic activities on diverse virome profiles, with R. tanezumi as an important reservoir for zoonotic viruses.
{"title":"Viral diversity in wild and urban rodents of Yunnan Province, China.","authors":"Yakhouba Kane, Alexander Tendu, Ruiya Li, Yanhua Chen, Emilio Mastriani, Jiaming Lan, Alice Catherine Hughes, Nicolas Berthet, Gary Wong","doi":"10.1080/22221751.2023.2290842","DOIUrl":"10.1080/22221751.2023.2290842","url":null,"abstract":"<p><p>Rodents represent over 40% of known mammal species and are found in various terrestrial habitats. They are significant reservoirs for zoonotic viruses, including harmful pathogens such as arenaviruses and hantaviruses, yet knowledge of their hosts and distributions is limited. Therefore, characterizing the virome profile in these animals is invaluable for outbreak preparedness, especially in potential hotspots of mammal diversity. This study included 681 organs from 124 rodents and one Chinese tree shrew collected from Yunnan Province, China, during 2020-2021. Metagenomic analysis revealed unique features of mammalian viruses in rodent organs across habitats with varying human disturbances. <i>R. tanezumi</i> in locations with high anthropogenic disturbance exhibited the highest mammal viral diversity, with spleen and lung samples showing the highest diversities for these viruses at the organ level. Mammal viral diversity for both commensal and non-commensal rats was identified to positively correlate with landscape disturbance. Some virus families were associated with particular organs or host species, suggesting tropism for these pathogens. Notably, known and novel viral species that are likely to infect humans were identified. <i>R. tanezumi</i> was identified as a reservoir and carrier for various zoonotic viruses, including porcine bocavirus, hantavirus, cardiovirus, and lyssavirus. These findings highlight the influence of rodent community composition and anthropogenic activities on diverse virome profiles, with <i>R. tanezumi</i> as an important reservoir for zoonotic viruses.</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/PMC10829829/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138477057","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}