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Search results for: Adenovirus

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#34523968   2021/09/15 To Up

Protective efficacy of rhesus adenovirus COVID-19 vaccines against mouse-adapted SARS-CoV-2.

The global COVID-19 pandemic has sparked intense interest in the rapid development of vaccines as well as animal models to evaluate vaccine candidates and to define immune correlates of protection. We recently reported a mouse-adapted SARS-CoV-2 virus strain (MA10) with the potential to infect wild-type laboratory mice, driving high levels of viral replication in respiratory tract tissues as well as severe clinical and respiratory symptoms, aspects of COVID-19 disease in humans that are important to capture in model systems. We evaluated the immunogenicity and protective efficacy of novel rhesus adenovirus serotype 52 (RhAd52) vaccines against MA10 challenge in mice. Baseline seroprevalence is lower for rhesus adenovirus vectors than for human or chimpanzee adenovirus vectors, making these vectors attractive candidates for vaccine development. We observed that RhAd52 vaccines elicited robust binding and neutralizing antibody titers, which inversely correlated with viral replication after challenge. These data support the development of RhAd52 vaccines and the use of the MA10 challenge virus to screen novel vaccine candidates and to study the immunologic mechanisms that underscore protection from SARS-CoV-2 challenge in wild-type mice. We have developed a series of SARS-CoV-2 vaccines using rhesus adenovirus serotype 52 (RhAd52) vectors, which exhibits a lower seroprevalence than human and chimpanzee vectors, supporting their development as novel vaccine vectors or as an alternative Ad vector for boosting. We sought to test these vaccines using a recently reported mouse-adapted SARS-CoV-2 (MA10) virus to i) evaluate the protective efficacy of RhAd52 vaccines and ii) further characterize this mouse-adapted challenge model and probe immune correlates of protection. We demonstrate RhAd52 vaccines elicit robust SARS-CoV-2-specific antibody responses and protect against clinical disease and viral replication in the lungs. Further, binding and neutralizing antibody titers correlated with protective efficacy. These data validate the MA10 mouse model as a useful tool to screen and study novel vaccine candidates, as well as the development of RhAd52 vaccines for COVID-19.
Lisa H Tostanoski, Lisa E Gralinski, David R Martinez, Alexandra Schaefer, Shant H Mahrokhian, Zhenfeng Li, Felix Nampanya, Huahua Wan, Jingyou Yu, Aiquan Chang, Jinyan Liu, Katherine McMahan, John D Ventura, Kenneth H Dinnon, Sarah R Leist, Ralph S Baric, Dan H Barouch

1802 related Products with: Protective efficacy of rhesus adenovirus COVID-19 vaccines against mouse-adapted SARS-CoV-2.

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#34523109   2021/09/15 To Up

A Multicenter Study of Viral Aetiology of Community-Acquired Pneumonia in Hospitalized Children in Chinese Mainland.

Community-acquired pneumonia (CAP) is one of the leading causes of morbidity and mortality in children worldwide. In this study, we aimed to describe the aetiology of viral infection of pediatric CAP in Chinese mainland. During November 2014 to June 2016, the prospective study was conducted in 13 hospitals. The hospitalized children under 18 years old who met the criteria for CAP were enrolled. The throat swabs or nasopharyngeal aspirates (NPAs) were collected which were then screened 18 respiratory viruses using multiplex PCR assay. Viral pathogens were present in 56.6% (1539/2721) of the enrolled cases, with the detection rate of single virus in 39.8% of the cases and multiple viruses in 16.8% of the cases. The most frequently detected virus was respiratory syncytial virus (RSV) (15.2%, 414/2721). The highest detection rate of virus was in < 6-month-age group (70.7%, 292/413). RSV, human metapneumovirus (HMPV), human parainfluenza viruses (HPIVs) and influenza B virus (Flu B) showed the similar prevalence patterns both in north and south China, but HPIVs, Flu A, human bocavirus (HBoV), human adenovirus (HAdV) and human coronaviruses (HCoVs) showed the distinct circulating patterns in north and south China. Human enterovirus/human rhinovirus (HEV/HRV) (27.6%, 27/98), HBoV (18.4%, 18/98), RSV (16.3%, 16/98) and HMPV (14.3%, 14/98) were the most commonly detected viruses in severe pneumonia cases with single virus infection. In conclusion, viral pathogens are frequently detected in pediatric CAP cases and may therefore play a vital role in the aetiology of CAP. RSV was the most important virus in hospitalized children with CAP in Chinese mainland.
Yun Zhu, Baoping Xu, Changchong Li, Zhimin Chen, Ling Cao, Zhou Fu, Yunxiao Shang, Aihuan Chen, Li Deng, Yixiao Bao, Yun Sun, Limin Ning, Shuilian Yu, Fang Gu, Chunyan Liu, Ju Yin, Adong Shen, Zhengde Xie, Kunling Shen

2950 related Products with: A Multicenter Study of Viral Aetiology of Community-Acquired Pneumonia in Hospitalized Children in Chinese Mainland.

150μg1 Set100.00 ug1 Set100 μg100 μg500 tests100 μg100 μg

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#34522441   2021/08/23 To Up

A "Prime and Deploy" Strategy for Universal Influenza Vaccine Targeting Nucleoprotein Induces Lung-Resident Memory CD8 T cells.

Lung-resident memory T cells (T) play an essential role in protecting against pulmonary virus infection. Parenteral administration of DNA vaccine is generally not sufficient to induce lung CD8 T cells. This study investigates whether intramuscularly administered DNA vaccine expressing the nucleoprotein (NP) induces lung T cells and protects against the influenza B virus. The results show that DNA vaccination poorly generates lung T cells and massive secondary effector CD8 T cells entering the lungs after challenge infection do not offer sufficient protection. Nonetheless, intranasal administration of non-replicating adenovirus vector expressing no Ag following priming DNA vaccination deploys NP-specific CD8 T cells in the lungs, which subsequently offers complete protection. This novel 'prime and deploy' strategy could be a promising regimen for a universal influenza vaccine targeting the conserved NP Ag.
Haerynn Chung, Eun-Ah Kim, Jun Chang

1706 related Products with: A "Prime and Deploy" Strategy for Universal Influenza Vaccine Targeting Nucleoprotein Induces Lung-Resident Memory CD8 T cells.

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#34520320   2021/09/14 To Up

A bivalent live-attenuated vaccine candidate elicits protective immunity against human adenovirus types 4 and 7.

Human adenovirus types 4 (HAdV4) and 7 (HAdV7) often lead to severe respiratory diseases and occur epidemically in children, adults, immune deficiency patients, and other groups, leading to mild or severe symptoms and even death. However, no licensed adenovirus vaccine has been approved in the market for general use. E3 genes of adenovirus are generally considered nonessential for virulence and replication; however, a few studies have demonstrated that the products of these genes are also functional. In this study, most of the E3 genes were deleted, and two E3-deleted recombinant adenoviruses (ΔE3-rAdVs) were constructed as components of the vaccine. After E3 deletion, the replication efficiencies and cytopathogenicity of ΔE3-rAdVs were reduced, indicating that ΔE3-rAdVs were attenuated after E3 genes deletion. Furthermore, single immunization with live-attenuated bivalent vaccine candidate protects mice against challenge with wild-type human adenovirus types 4 and 7, respectively. Vaccinated mice demonstrated remarkably decreased viral loads in the lungs and less lung pathology compared to the control animals. Taken together, our study confirms the possibility of the two live-attenuated viruses as a vaccine for clinic use and illustrates a novel strategy for the construction of an adenovirus vaccine.
Jingao Guo, Youbin Zhang, Yan Zhang, Chao Zhang, Caihong Zhu, Man Xing, Xiang Wang, Dongming Zhou

2072 related Products with: A bivalent live-attenuated vaccine candidate elicits protective immunity against human adenovirus types 4 and 7.

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#34518841   2021/09/07 To Up

Immunogenicity of Pfizer mRNA COVID-19 vaccination followed by J&J adenovirus COVID-19 vaccination in two CLL patients.

Individuals with Chronic Lymphocytic Leukemia have significant immune disfunction, often further disrupted by treatment. While currently available COVID-19 vaccinations are highly effective in immunocompetent individuals, they are often poorly immunogenic in CLL patients. It is important to understand the role heterologous boost would have in patients who did not respond to the recommended two-dose mRNA vaccine series with a SARS-CoV-2 specific immune response.
Zoe L Lyski, Sunny Kim, David Xthona Lee, David Sampson, Hans P Raué, Vikram Raghunathan, Debbie Ryan, Amanda E Brunton, Mark K Slifka, William B Messer, Stephen E Spurgeon

1598 related Products with: Immunogenicity of Pfizer mRNA COVID-19 vaccination followed by J&J adenovirus COVID-19 vaccination in two CLL patients.

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#34516365   // To Up

Improved diagnosis of gastrointestinal infections using a semi-automated multiplex real-time PCR for detection of enteropathogens.

The identification of enteropathogens is critical for the clinical management of patients with suspected gastrointestinal infection. The FLOW multiplex PCR system (FMPS) is a semi-automated platform (FLOW System, Roche) for multiplex real-time PCR analysis. FMPS has greater sensitivity for the detection of enteric pathogens than standard methods such as culture, biochemical identification, immunochromatography or microscopic examination.The diagnostic performance of the FMPS was evaluated and compared to that of traditional microbiological procedures. A total of 10 659 samples were collected and analysed over a period of 7 years. From 2013 to 2018 (every July to September), samples were processed using standard microbiological culture methods. In 2019, the FMPS was implemented using real-time PCR to detect the following enteropathogens: spp. spp. spp., spp., adenovirus, norovirus and rotavirus. Standard microbiological culture methods (2013-2018) included stool culture, microscopy and immunochromatography. A total of 1078 stool samples were analysed prospectively using the FMPS from July to September (2019): bacterial, parasitic and viral pathogens were identified in 15.3, 9.71 and 5.29 % of cases, respectively. During the same period of 6 years (2013-2018), the proportion of positive identifications using standard microbiological methods from 2013 to 2018 was significantly lower. A major significant recovery improvement was observed for all bacteria species tested: spp./enteroinvasive (EIEC) ( <0.05), spp. ( <0.05) and spp. ( <0.05). Marked differences were also observed for the parasites , spp. and . These results support the value of multiplex real-time PCR analysis for the detection of enteric pathogens in laboratory diagnosis with outstanding performance in identifying labile micro-organisms. The identification of unsuspected micro-organisms for less specific clinical presentations may also impact on clinical practice and help optimize patient management.
Berta Fidalgo, Elisa Rubio, Victor Pastor, Marta Parera, Clara Ballesté-Delpierre, Mariana José Fernández, Genoveva Cuesta Chasco, Andrea Vergara, Yuliya Zboromyrska, Cristian Aylagas, Pilar Salvador, Adán Fernández, M Eugenia Valls, Míriam José Alvarez Martinez, Aurea Mira, Maria Angeles Marcos, Jordi Vila, Miguel J Martinez, Climent Casals-Pascual

2148 related Products with: Improved diagnosis of gastrointestinal infections using a semi-automated multiplex real-time PCR for detection of enteropathogens.

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#34516328   // To Up

CTRP6(C1q/Tumor Necrosis Factor (TNF)-related protein-6) alleviated the sevoflurane induced injury of mice central nervous system by promoting the expression of p-Akt (phosphorylated Akt).

Postoperative cognitive impairment and nervous system damage caused by anesthetics seriously affect patient's postoperative recovery. Recent study has revealed that CTRP6 could alleviate apoptosis, inflammation and oxidative stress of nerve cells, thereby relieving nervous system damage induced by cerebral ischemia reperfusion. However, whether CTRP6 could relieve sevoflurane induced central nervous system injury is unclear. We stimulated C57BL/6 mice with sevoflurane and injected CTRP6 overexpression adenovirus vector. Next, H&E staining and TUNEL assays were performed to examine the effect of CTRP6 on sevoflurane induced injury of central nervous system. Finally, we isolated primary nerve cells of hippocampus. Flow cytometry and commercial kits were used for the detection of apoptosis and ROS levels of these cells. Western blotting was used for the detection of the expression level of p-Akt in central nervous tissues and primary cells. Results showed that sevoflurane induced injury and apoptosis of central nervous tissues. Overexpression of CTRP6 relieved apoptosis and injury of these tissues. CTRP6 inhibited the expression of cleaved caspase-3 and cleaved PARP in these tissues. Sevoflurane promoted apoptosis of primary cells and enhanced the expression of ROS and MDA in these cells. Overexpression of CTRP6 alleviated apoptosis and suppressed production of ROS and MDA in these cells. In addition, CTRP6 also enhanced the expression of p-Akt in primary cells. Taken together, our results suggested that CTRP6 relieved sevoflurane induced injury of central nervous tissues by promoting the expression of p-Akt. Therefore, the targeted drug of CTRP6 should be explored for the remission of these symptoms.
Zhiwen Liu, Bin Yang

2476 related Products with: CTRP6(C1q/Tumor Necrosis Factor (TNF)-related protein-6) alleviated the sevoflurane induced injury of mice central nervous system by promoting the expression of p-Akt (phosphorylated Akt).

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#34516017   2021/09/13 To Up

Viral Kinetics and Outcomes of Adenovirus Viremia following Allogeneic Hematopoietic Cell Transplantation.

Adenovirus (AdV) is a serious infection following hematopoietic cell transplantation (HCT). Little is known about AdV viral kinetics and optimal threshold for initiation of pre-emptive therapy.
Aditya Chandorkar, Anthony D Anderson, Michele I Morris, Yoichiro Natori, Antonio Jimenez, Krishna V Komanduri, Jose F Camargo

1825 related Products with: Viral Kinetics and Outcomes of Adenovirus Viremia following Allogeneic Hematopoietic Cell Transplantation.

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#34515899   2021/09/13 To Up

Landscape Seroprevalence of Three Hemorrhagic Disease-Causing Viruses in a Wild Cervid.

Disease plays a major role in shaping wildlife populations worldwide, and changes in landscape conditions can significantly influence risk of pathogen exposure, a threat to vulnerable wild species. Three viruses that cause hemorrhagic disease affect cervid populations in the USA (Odocoileus hemionus adenovirus, bluetongue virus, and epizootic hemorrhagic disease virus), but little is known of their distribution and prevalence in wild populations. We explored the distribution and co-occurrence of seroprevalence of these three pathogens in southern mule deer (Odocoileus hemionus fuliginatus), a subspecies of conservation concern and a harvested species native to southern California, to evaluate the distribution of exposure to these pathogens relative to landscape attributes. We found that habitat type, level of development, and proximity to livestock may affect hemorrhagic disease seroprevalence in southern mule deer. Continued monitoring of hemorrhagic disease-causing viruses in areas where deer are in proximity to cattle and human development is needed to better understand the implications of future outbreaks in wild populations and to identify opportunities to mitigate disease impacts in southern mule deer and other cervid species.
Emma Tomaszewski, Megan Jennings, Brandon Munk, Randy Botta, Rebecca Lewison

1163 related Products with: Landscape Seroprevalence of Three Hemorrhagic Disease-Causing Viruses in a Wild Cervid.

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#34515675   2021/08/25 To Up

Defining Gene Functions in Tumorigenesis by Ex vivo Ablation of Floxed Alleles in Malignant Peripheral Nerve Sheath Tumor Cells.

The development of new drugs that precisely target key proteins in human cancers is fundamentally altering cancer therapeutics. However, before these drugs can be used, their target proteins must be validated as therapeutic targets in specific cancer types. This validation is often performed by knocking out the gene encoding the candidate therapeutic target in a genetically engineered mouse (GEM) model of cancer and determining what effect this has on tumor growth. Unfortunately, technical issues such as embryonic lethality in conventional knockouts and mosaicism in conditional knockouts often limit this approach. To overcome these limitations, an approach to ablating a floxed embryonic lethal gene of interest in short-term cultures of malignant peripheral nerve sheath tumors (MPNSTs) generated in a GEM model was developed. This paper describes how to establish a mouse model with the appropriate genotype, derive short-term tumor cultures from these animals, and then ablate the floxed embryonic lethal gene using an adenoviral vector that expresses Cre recombinase and enhanced green fluorescent protein (eGFP). Purification of cells transduced with adenovirus using fluorescence-activated cell sorting (FACS) and the quantification of the effects that gene ablation exerts on cellular proliferation, viability, the transcriptome, and orthotopic allograft growth is then detailed. These methodologies provide an effective and generalizable approach to identifying and validating therapeutic targets in vitro and in vivo. These approaches also provide a renewable source of low-passage tumor-derived cells with reduced in vitro growth artifacts. This allows the biological role of the targeted gene to be studied in diverse biologic processes such as migration, invasion, metastasis, and intercellular communication mediated by the secretome.
Jody Fromm Longo, Stephanie N Brosius, Steven L Carroll

2151 related Products with: Defining Gene Functions in Tumorigenesis by Ex vivo Ablation of Floxed Alleles in Malignant Peripheral Nerve Sheath Tumor Cells.

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