Pub Date : 2024-12-01Epub Date: 2024-07-15DOI: 10.1080/22221751.2024.2373309
Shuting Huo, Leyun Wu, Baoying Huang, Nan Liu, Jiewei Sun, Fei Ye, Yao Deng, Jing Chen, Likun Gong, Weiliang Zhu, Zhijian Xu, Wenjie Tan
{"title":"Identification of the VP37 pocket of monkeypox virus as a promising target for pan-orthopoxvirus inhibitors through virtual screening and antiviral assays.","authors":"Shuting Huo, Leyun Wu, Baoying Huang, Nan Liu, Jiewei Sun, Fei Ye, Yao Deng, Jing Chen, Likun Gong, Weiliang Zhu, Zhijian Xu, Wenjie Tan","doi":"10.1080/22221751.2024.2373309","DOIUrl":"10.1080/22221751.2024.2373309","url":null,"abstract":"","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/PMC11251428/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141450085","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: 2024-08-12DOI: 10.1080/22221751.2024.2384460
Roger Tatoud, Christian Brander, Carey Hwang, Jo Kennelly, Shan Lu, Kevin O'Neil, Jeffrey T Safrit, Iris Benhayoun, Julieta Firmat, Nelli Barriere
HIV vaccine development has been hindered by significant challenges over four decades. Despite persistent efforts, all efficacy trials to date have yielded disappointing results. This has pushed the field back to the discovery phase and created uncertainty about the future involvement of large pharmaceutical companies. Currently, the HIV vaccine landscape is dominated by startup biotech firms, which face a complex array of obstacles. These include evolving HIV prevention methods, waning interest in vaccine research, and difficulties securing sustainable funding. This viewpoint explores the challenges faced by these biotech companies and the support mechanisms necessary for their continued involvement in HIV vaccine development. By leveraging insights from both pharmaceutical and biotech sectors, we propose a multi-faceted approach that includes enhanced communication, fostering innovation, and implementing strategic funding models.
{"title":"Biotech's role in advancing HIV vaccine development.","authors":"Roger Tatoud, Christian Brander, Carey Hwang, Jo Kennelly, Shan Lu, Kevin O'Neil, Jeffrey T Safrit, Iris Benhayoun, Julieta Firmat, Nelli Barriere","doi":"10.1080/22221751.2024.2384460","DOIUrl":"10.1080/22221751.2024.2384460","url":null,"abstract":"<p><p>HIV vaccine development has been hindered by significant challenges over four decades. Despite persistent efforts, all efficacy trials to date have yielded disappointing results. This has pushed the field back to the discovery phase and created uncertainty about the future involvement of large pharmaceutical companies. Currently, the HIV vaccine landscape is dominated by startup biotech firms, which face a complex array of obstacles. These include evolving HIV prevention methods, waning interest in vaccine research, and difficulties securing sustainable funding. This viewpoint explores the challenges faced by these biotech companies and the support mechanisms necessary for their continued involvement in HIV vaccine development. By leveraging insights from both pharmaceutical and biotech sectors, we propose a multi-faceted approach that includes enhanced communication, fostering innovation, and implementing strategic funding models.</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/PMC11321102/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141747754","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}
Mycobacterium chelonae and Sporothrix globosa, both of which are opportunistic pathogens, have been proved to be possible multidrug resistant. However, are all recurring symptoms in chronic infections related to decreasing susceptibility? Here we report a case of sporotrichosis secondary to M. chelonae infection. In addition, we find that the blackish-red spots under the dermoscopic view can be employed as a signal for the early identification and regression of subcutaneous fungal infection.
{"title":"Disasters pile up on the rubbing heel: <i>Sporothrix globosa</i> as secondary infection to <i>Mycobacterium chelonae</i> infection.","authors":"Zhi Zhang, Lina Li, Hongsheng Wang, Xin Ran, Yuan Chen, Xinyao Liu, Yuping Ran","doi":"10.1080/22221751.2024.2358073","DOIUrl":"10.1080/22221751.2024.2358073","url":null,"abstract":"<p><p><i>Mycobacterium chelonae</i> and <i>Sporothrix globosa</i>, both of which are opportunistic pathogens, have been proved to be possible multidrug resistant. However, are all recurring symptoms in chronic infections related to decreasing susceptibility? Here we report a case of sporotrichosis secondary to <i>M. chelonae</i> infection. In addition, we find that the blackish-red spots under the dermoscopic view can be employed as a signal for the early identification and regression of subcutaneous fungal infection.</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/PMC11168209/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141065032","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: 2024-09-09DOI: 10.1080/22221751.2024.2398596
Sufei Tian, Chen Rong, Hailong Li, Yusheng Wu, Na Wu, Yunzhuo Chu, Ning Jiang, Jingping Zhang, Hong Shang
The global rate of Amphotericin B (AmB) resistance in Candida auris has surpassed 12%. However, there is limited data on available clinical treatments and microevolutionary analyses concerning reduced AmB sensitivity. In this study, we collected 18 C. auris isolates from five patients between 2019 and 2022. We employed clinical data mining, genomic, and transcriptomic analyses to identify genetic evolutionary features linked to reduced AmB sensitivity in these isolates during clinical treatment. We identified six isolates with a minimum inhibitory concentration (MIC) of AmB below 0.5 µg/mL (AmB0.5) and 12 isolates with an AmB-MIC of 1 µg/mL (AmB1) or ≥ 2 µg/mL (AmB2). All five patients received 24-hour AmB (5 mg/L) bladder irrigation treatment. Evolutionary analyses revealed an ERG3 (c923t) mutation in AmB1C. auris. Additionally, AmB2C. auris was found to contain a t2831c mutation in the RAD2 gene. In the AmB1 group, membrane lipid-related gene expression (ERG1, ERG2, ERG13, and ERG24) was upregulated, while in the AmB2 group, expression of DNA-related genes (e.g. DNA2 and PRI1) was up-regulated. In a series of C.auris strains with reduced susceptibility to AmB, five key genes were identified: two upregulated (IFF9 and PGA6) and three downregulated (HGT7, HGT13,and PRI32). In this study, we demonstrate the microevolution of reduced AmB sensitivity in vivo and further elucidate the relationship between reduced AmB sensitivity and low-concentration AmB bladder irrigation. These findings offer new insights into potential antifungal drug targets and clinical markers for the "super fungus", C. auris.
全球白色念珠菌对两性霉素 B(AmB)的耐药率已超过 12%。然而,现有的临床治疗数据和关于AmB敏感性降低的微进化分析却很有限。在本研究中,我们从 2019 年至 2022 年期间的五名患者中收集了 18 个念珠菌分离株。我们采用临床数据挖掘、基因组和转录组分析来确定这些分离株在临床治疗期间与AmB敏感性降低相关的基因进化特征。我们发现了6株AmB最低抑菌浓度(MIC)低于0.5微克/毫升(AmB0.5)的分离株和12株AmB-MIC为1微克/毫升(AmB1)或≥2微克/毫升(AmB2)的分离株。所有五名患者都接受了 24 小时 AmB(5 毫克/升)膀胱冲洗治疗。进化分析表明,AmB1 C. auris 中存在 ERG3(c923t)突变。此外,还发现 AmB2 C. auris 包含 RAD2 基因 t2831c 突变。在 AmB1 组中,膜脂质相关基因(ERG1、ERG2、ERG13 和 ERG24)的表达上调,而在 AmB2 组中,DNA 相关基因(如 DNA2 和 PRI1)的表达上调。在一系列对 AmB 敏感性降低的 C.auris 菌株中,发现了五个关键基因:两个上调(IFF9 和 PGA6),三个下调(HGT7、HGT13 和 PRI32)。在这项研究中,我们证明了体内 AmB 敏感性降低的微观演变,并进一步阐明了 AmB 敏感性降低与低浓度 AmB 膀胱灌注之间的关系。这些发现为 "超级真菌 "C. auris 的潜在抗真菌药物靶点和临床标记物提供了新的见解。
{"title":"Genetic microevolution of clinical <i>Candida auris</i> with reduced Amphotericin B sensitivity in China.","authors":"Sufei Tian, Chen Rong, Hailong Li, Yusheng Wu, Na Wu, Yunzhuo Chu, Ning Jiang, Jingping Zhang, Hong Shang","doi":"10.1080/22221751.2024.2398596","DOIUrl":"10.1080/22221751.2024.2398596","url":null,"abstract":"<p><p>The global rate of Amphotericin B (AmB) resistance in <i>Candida auris</i> has surpassed 12%. However, there is limited data on available clinical treatments and microevolutionary analyses concerning reduced AmB sensitivity. In this study, we collected 18 <i>C. auris</i> isolates from five patients between 2019 and 2022. We employed clinical data mining, genomic, and transcriptomic analyses to identify genetic evolutionary features linked to reduced AmB sensitivity in these isolates during clinical treatment. We identified six isolates with a minimum inhibitory concentration (MIC) of AmB below 0.5 µg/mL (AmB<sup>0.5</sup>) and 12 isolates with an AmB-MIC of 1 µg/mL (AmB<sup>1</sup>) or ≥ 2 µg/mL (AmB<sup>2</sup>). All five patients received 24-hour AmB (5 mg/L) bladder irrigation treatment. Evolutionary analyses revealed an <i>ERG3</i> (c923t) mutation in AmB<sup>1</sup> <i>C. auris</i>. Additionally, AmB<sup>2</sup> <i>C. auris</i> was found to contain a t2831c mutation in the <i>RAD2</i> gene. In the AmB<sup>1</sup> group, membrane lipid-related gene expression (<i>ERG1, ERG2, ERG13,</i> and <i>ERG24</i>) was upregulated, while in the AmB<sup>2</sup> group, expression of DNA-related genes (e.g. <i>DNA2</i> and <i>PRI1</i>) was up-regulated. In a series of <i>C.auris</i> strains with reduced susceptibility to AmB, five key genes were identified: two upregulated (<i>IFF9</i> and <i>PGA6)</i> and three downregulated (<i>HGT7, HGT13,</i>and <i>PRI32)</i>. In this study, we demonstrate the microevolution of reduced AmB sensitivity in vivo and further elucidate the relationship between reduced AmB sensitivity and low-concentration AmB bladder irrigation. These findings offer new insights into potential antifungal drug targets and clinical markers for the \"super fungus\", <i>C. auris</i>.</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":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142132172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The persistence of HBV covalently closed circular DNA (cccDNA) and HBV integration into the host genome in infected hepatocytes pose significant challenges to the cure of chronic HBV infection. Although CRISPR/Cas9-mediated genome editing shows promise for targeted clearance of viral genomes, a safe and efficient delivery method is currently lacking. Here, we developed a novel approach by combining light-induced heterodimerization and protein acylation to enhance the loading efficiency of Cas9 protein into extracellular vesicles (EVs). Moreover, vesicular stomatitis virus-glycoprotein (VSV-G) was incorporated onto the EVs membrane, significantly facilitating the endosomal escape of Cas9 protein and increasing its gene editing activity in recipient cells. Our results demonstrated that engineered EVs containing Cas9/gRNA and VSV-G can effectively reduce viral antigens and cccDNA levels in the HBV-replicating and infected cell models. Notably, we also confirmed the antiviral activity and high safety of the engineered EVs in the HBV-replicating mouse model generated by hydrodynamic injection and the HBV transgenic mouse model. In conclusion, engineered EVs could successfully mediate functional CRISPR/Cas9 delivery both in vitro and in vivo, leading to the clearance of episomal cccDNA and integrated viral DNA fragments, and providing a novel therapeutic approach for curing chronic HBV infection.
{"title":"Engineered extracellular vesicles for delivering functional Cas9/gRNA to eliminate hepatitis B virus cccDNA and integration.","authors":"Wanjia Zeng, Liwei Zheng, Yukun Li, Jing Yang, Tianhao Mao, Jing Zhang, Yanna Liu, Jing Ning, Ting Zhang, Hongxin Huang, Xiangmei Chen, Fengmin Lu","doi":"10.1080/22221751.2023.2284286","DOIUrl":"10.1080/22221751.2023.2284286","url":null,"abstract":"<p><p>The persistence of HBV covalently closed circular DNA (cccDNA) and HBV integration into the host genome in infected hepatocytes pose significant challenges to the cure of chronic HBV infection. Although CRISPR/Cas9-mediated genome editing shows promise for targeted clearance of viral genomes, a safe and efficient delivery method is currently lacking. Here, we developed a novel approach by combining light-induced heterodimerization and protein acylation to enhance the loading efficiency of Cas9 protein into extracellular vesicles (EVs). Moreover, vesicular stomatitis virus-glycoprotein (VSV-G) was incorporated onto the EVs membrane, significantly facilitating the endosomal escape of Cas9 protein and increasing its gene editing activity in recipient cells. Our results demonstrated that engineered EVs containing Cas9/gRNA and VSV-G can effectively reduce viral antigens and cccDNA levels in the HBV-replicating and infected cell models. Notably, we also confirmed the antiviral activity and high safety of the engineered EVs in the HBV-replicating mouse model generated by hydrodynamic injection and the HBV transgenic mouse model. In conclusion, engineered EVs could successfully mediate functional CRISPR/Cas9 delivery both <i>in vitro</i> and <i>in vivo</i>, leading to the clearance of episomal cccDNA and integrated viral DNA fragments, and providing a novel therapeutic approach for curing chronic HBV infection.</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/PMC10763861/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138046639","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: 10.1080/22221751.2023.2287682
Dexin Kong, Yanjuan He, Jiaxin Wang, Lanyan Chi, Xiang Ao, Hejia Ye, Weihong Qiu, Xiutong Zhu, Ming Liao, Huiying Fan
The H5N1 subtype highly pathogenic avian influenza virus (HPAIV) reveals high variability and threatens poultry production and public health. To prevent the spread of H5N1 HPAIV, we developed an H5N1 virus-like particle (VLP) vaccine based on the insect cell-baculovirus expression system. Single immunization of the H5N1 VLP vaccines induced high levels of HI antibody titres and provided effective protection against homologous virus challenge comparable to the commercial inactivated vaccine. Meanwhile, we assessed the relative efficacy of different adjuvants by carrying out a head-to-head comparison of the adjuvants ISA 201 and ISA 71 and evaluated whether the two adjuvants could induce broadly protective immunity. The ISA 71 adjuvanted vaccine induced significantly higher levels of Th1 and Th2 immune responses and provided superior cross-protection against antigenically divergent H5N1 virus challenge than the ISA 201 adjuvanted vaccine. Importantly, increasing the vaccine dose could further enhance the cross-protective efficacy of H5N1 VLP vaccine and confer completely sterilizing protection against antigenically divergent H5N1 virus challenge, which was mediated by neutralizing antibodies. Our results suggest that the H5N1 VLP vaccine can provide broad-spectrum protection against divergent H5N1 influenza viruses as determined by adjuvant and vaccine dose.
{"title":"A single immunization with H5N1 virus-like particle vaccine protects chickens against divergent H5N1 influenza viruses and vaccine efficacy is determined by adjuvant and dosage.","authors":"Dexin Kong, Yanjuan He, Jiaxin Wang, Lanyan Chi, Xiang Ao, Hejia Ye, Weihong Qiu, Xiutong Zhu, Ming Liao, Huiying Fan","doi":"10.1080/22221751.2023.2287682","DOIUrl":"10.1080/22221751.2023.2287682","url":null,"abstract":"<p><p>The H5N1 subtype highly pathogenic avian influenza virus (HPAIV) reveals high variability and threatens poultry production and public health. To prevent the spread of H5N1 HPAIV, we developed an H5N1 virus-like particle (VLP) vaccine based on the insect cell-baculovirus expression system. Single immunization of the H5N1 VLP vaccines induced high levels of HI antibody titres and provided effective protection against homologous virus challenge comparable to the commercial inactivated vaccine. Meanwhile, we assessed the relative efficacy of different adjuvants by carrying out a head-to-head comparison of the adjuvants ISA 201 and ISA 71 and evaluated whether the two adjuvants could induce broadly protective immunity. The ISA 71 adjuvanted vaccine induced significantly higher levels of Th1 and Th2 immune responses and provided superior cross-protection against antigenically divergent H5N1 virus challenge than the ISA 201 adjuvanted vaccine. Importantly, increasing the vaccine dose could further enhance the cross-protective efficacy of H5N1 VLP vaccine and confer completely sterilizing protection against antigenically divergent H5N1 virus challenge, which was mediated by neutralizing antibodies. Our results suggest that the H5N1 VLP vaccine can provide broad-spectrum protection against divergent H5N1 influenza viruses as determined by adjuvant and vaccine dose.</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/PMC10763850/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138294928","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: 2024-02-06DOI: 10.1080/22221751.2023.2292071
Jianpeng Cai, Haocheng Zhang, Kun Zhu, Feng Zhu, Yan Wang, Sen Wang, Faren Xie, Meng Zhang, Lili Rui, Shuhong Li, Ke Lin, Quanlin Xue, Guanmin Yuan, Hongyu Wang, Yi Zhang, Zhangfan Fu, Jieyu Song, Yanliang Zhang, Jingwen Ai, Wenhong Zhang
Data on reinfection in large Asian populations are limited. In this study, we aimed to evaluate the reinfection rate, disease severity, and time interval between the infections in the symptomatic and asymptomatic populations which are firstl infected with BA.2 Omicron Variant. We retrospectively included adult patients with COVID-19 discharged from four designated hospitals between 27 April 2021 and 30 November 2022, who were interviewed via telephone from 29 January to 1 March 2023. Univariable and multivariable analyses were used to explore risk factors associated with reinfection. A total of 16,558 patients were followed up, during the telephone survey of an average of 310.0 days, 1610 (9.72%) participants self-reported reinfection. The mean time range of reinfection was 257.9 days. The risks for reinfection were analysed using multivariable logistic regression. Patients with severe first infection were at higher risk for reinfection (aORs, 2.50; P < 0.001). The male (aORs,0.82; P < 0.001), the elderly (aORs, 0.44; P < 0.001), and patients with full vaccination (aORs, 0.67; P < 0.001) or booster (aORs, 0.63; P < 0.001) had the lower risk of reinfection. Patients over 60 years of age (aORs,9.02; P = 0.006) and those with ≥2 comorbidities (aORs,11.51; P = 0.016). were at higher risk for severe reinfection. The number of clinical manifestations of reinfection increases in people with severe first infection (aORs, 2.82; P = 0.023). The overall reinfection rate was 9.72%, and the reinfection rate of Omicron-to-Omicron subvariants was 9.50% at one year. The severity of Omicron-Omicron reinfection decreased. Data from our clinical study may provide clinical evidence and bolster response preparedness for future COVID-19 reinfection waves.
{"title":"Risk of reinfection and severity with the predominant BA.5 Omicron subvariant China, from December 2022 to January 2023.","authors":"Jianpeng Cai, Haocheng Zhang, Kun Zhu, Feng Zhu, Yan Wang, Sen Wang, Faren Xie, Meng Zhang, Lili Rui, Shuhong Li, Ke Lin, Quanlin Xue, Guanmin Yuan, Hongyu Wang, Yi Zhang, Zhangfan Fu, Jieyu Song, Yanliang Zhang, Jingwen Ai, Wenhong Zhang","doi":"10.1080/22221751.2023.2292071","DOIUrl":"10.1080/22221751.2023.2292071","url":null,"abstract":"<p><p>Data on reinfection in large Asian populations are limited. In this study, we aimed to evaluate the reinfection rate, disease severity, and time interval between the infections in the symptomatic and asymptomatic populations which are firstl infected with BA.2 Omicron Variant. We retrospectively included adult patients with COVID-19 discharged from four designated hospitals between 27 April 2021 and 30 November 2022, who were interviewed via telephone from 29 January to 1 March 2023. Univariable and multivariable analyses were used to explore risk factors associated with reinfection. A total of 16,558 patients were followed up, during the telephone survey of an average of 310.0 days, 1610 (9.72%) participants self-reported reinfection. The mean time range of reinfection was 257.9 days. The risks for reinfection were analysed using multivariable logistic regression. Patients with severe first infection were at higher risk for reinfection (aORs, 2.50; <i>P</i> < 0.001). The male (aORs,0.82; <i>P</i> < 0.001), the elderly (aORs, 0.44; <i>P</i> < 0.001), and patients with full vaccination (aORs, 0.67; <i>P</i> < 0.001) or booster (aORs, 0.63; <i>P</i> < 0.001) had the lower risk of reinfection. Patients over 60 years of age (aORs,9.02; <i>P</i> = 0.006) and those with ≥2 comorbidities (aORs,11.51; <i>P</i> = 0.016). were at higher risk for severe reinfection. The number of clinical manifestations of reinfection increases in people with severe first infection (aORs, 2.82; <i>P</i> = 0.023). The overall reinfection rate was 9.72%, and the reinfection rate of Omicron-to-Omicron subvariants was 9.50% at one year. The severity of Omicron-Omicron reinfection decreased. Data from our clinical study may provide clinical evidence and bolster response preparedness for future COVID-19 reinfection waves.</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/PMC10849001/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138487005","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}
Vaccines utilizing modified messenger RNA (mRNA) technology have shown robust protective efficacy against SARS-CoV-2 in humans. As the virus continues to evolve in both human and non-human hosts, risk remains that the performance of the vaccines can be compromised by new variants with strong immune escape abilities. Here we present preclinical characterizations of a novel bivalent mRNA vaccine RQ3025 for its safety and effectiveness in animal models. The mRNA sequence of the vaccine is designed to incorporate common mutations on the SARS-CoV-2 spike protein that have been discovered along the evolutionary paths of different variants. Broad-spectrum, high-titer neutralizing antibodies against multiple variants were induced in mice (BALB/c and K18-hACE2), hamsters and rats upon injections of RQ3025, demonstrating advantages over the monovalent mRNA vaccines. Effectiveness in protection against several newly emerged variants is also evident in RQ3025-vaccinated rats. Analysis of splenocytes derived cytokines in BALB/c mice suggested that a Th1-biased cellular immune response was induced by RQ3025. Histological analysis of multiple organs in rats following injection of a high dose of RQ3025 showed no evidence of pathological changes. This study proves the safety and effectiveness of RQ3025 as a broad-spectrum vaccine against SARS-CoV-2 variants in animal models and lays the foundation for its potential clinical application in the future.
{"title":"Effectiveness of a broad-spectrum bivalent mRNA vaccine against SARS-CoV-2 variants in preclinical studies.","authors":"Jing Lu, Shudan Tan, Hao Gu, Kunpeng Liu, Wei Huang, Zhaoli Yu, Guoliang Lu, Zihan Wu, Xiaobo Gao, Jinghua Zhao, Zongting Yao, Feng Yi, Yantao Yang, Hu Wang, Xue Hu, Mingqing Lu, Wei Li, Hui Zhou, Hang Yu, Chao Shan, Jinzhong Lin","doi":"10.1080/22221751.2024.2321994","DOIUrl":"10.1080/22221751.2024.2321994","url":null,"abstract":"<p><p>Vaccines utilizing modified messenger RNA (mRNA) technology have shown robust protective efficacy against SARS-CoV-2 in humans. As the virus continues to evolve in both human and non-human hosts, risk remains that the performance of the vaccines can be compromised by new variants with strong immune escape abilities. Here we present preclinical characterizations of a novel bivalent mRNA vaccine RQ3025 for its safety and effectiveness in animal models. The mRNA sequence of the vaccine is designed to incorporate common mutations on the SARS-CoV-2 spike protein that have been discovered along the evolutionary paths of different variants. Broad-spectrum, high-titer neutralizing antibodies against multiple variants were induced in mice (BALB/c and K18-hACE2), hamsters and rats upon injections of RQ3025, demonstrating advantages over the monovalent mRNA vaccines. Effectiveness in protection against several newly emerged variants is also evident in RQ3025-vaccinated rats. Analysis of splenocytes derived cytokines in BALB/c mice suggested that a Th1-biased cellular immune response was induced by RQ3025. Histological analysis of multiple organs in rats following injection of a high dose of RQ3025 showed no evidence of pathological changes. This study proves the safety and effectiveness of RQ3025 as a broad-spectrum vaccine against SARS-CoV-2 variants in animal models and lays the foundation for its potential clinical application in the future.</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/PMC10906132/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139912342","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}
Streptococcus suis is a major bacterial pathogen in pigs and an emerging zoonotic pathogen. Different S. suis serotypes exhibit diverse characteristics in population structure and pathogenicity. Surveillance data highlight the significance of S. suis serotype 4 (SS4) in swine streptococcusis, a pathotype causing human infections. However, except for a few epidemiologic studies, the information on SS4 remains limited. In this study, we investigated the population structure, pathogenicity, and antimicrobial characteristics of SS4 based on 126 isolates, including one from a patient with septicemia. We discovered significant diversities within this population, clustering into six minimum core genome (MCG) groups (1, 2, 3, 4, 7-2, and 7-3) and five lineages. Two main clonal complexes (CCs), CC17 and CC94, belong to MCG groups 1 and 3, respectively. Numerous important putative virulence-associated genes are present in these two MCG groups, and 35.00% (7/20) of pig isolates from CC17, CC94, and CC839 (also belonging to MCG group 3) were highly virulent (mortality rate ≥ 80%) in zebrafish and mice, similar to the human isolate ID36054. Cytotoxicity assays showed that the human and pig isolates of SS4 strains exhibit significant cytotoxicity to human cells. Antimicrobial susceptibility testing showed that 95.83% of strains isolated from our labs were classified as multidrug-resistant. Prophages were identified as the primary vehicle for antibiotic resistance genes. Our study demonstrates the public health threat posed by SS4, expanding the understanding of SS4 population structure and pathogenicity characteristics and providing valuable information for its surveillance and prevention.
{"title":"<i>Streptococcus suis</i> serotype 4: a population with the potential pathogenicity in humans and pigs.","authors":"Jinlu Zhu, Jianping Wang, Weiming Kang, Xiyan Zhang, Anusak Kerdsin, Huochun Yao, Han Zheng, Zongfu Wu","doi":"10.1080/22221751.2024.2352435","DOIUrl":"10.1080/22221751.2024.2352435","url":null,"abstract":"<p><p><i>Streptococcus suis</i> is a major bacterial pathogen in pigs and an emerging zoonotic pathogen. Different <i>S. suis</i> serotypes exhibit diverse characteristics in population structure and pathogenicity. Surveillance data highlight the significance of <i>S. suis</i> serotype 4 (SS4) in swine streptococcusis, a pathotype causing human infections. However, except for a few epidemiologic studies, the information on SS4 remains limited. In this study, we investigated the population structure, pathogenicity, and antimicrobial characteristics of SS4 based on 126 isolates, including one from a patient with septicemia. We discovered significant diversities within this population, clustering into six minimum core genome (MCG) groups (1, 2, 3, 4, 7-2, and 7-3) and five lineages. Two main clonal complexes (CCs), CC17 and CC94, belong to MCG groups 1 and 3, respectively. Numerous important putative virulence-associated genes are present in these two MCG groups, and 35.00% (7/20) of pig isolates from CC17, CC94, and CC839 (also belonging to MCG group 3) were highly virulent (mortality rate ≥ 80%) in zebrafish and mice, similar to the human isolate ID36054. Cytotoxicity assays showed that the human and pig isolates of SS4 strains exhibit significant cytotoxicity to human cells. Antimicrobial susceptibility testing showed that 95.83% of strains isolated from our labs were classified as multidrug-resistant. Prophages were identified as the primary vehicle for antibiotic resistance genes. Our study demonstrates the public health threat posed by SS4, expanding the understanding of SS4 population structure and pathogenicity characteristics and providing valuable information for its surveillance and prevention.</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/PMC11097711/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140848152","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}