Virus nomenclature below the species level: a standardized nomenclature for laboratory animal-adapted strains and variants of viruses assigned to the family Filoviridae
Abstract:The International Committee on Taxonomy of Viruses (ICTV) organizes the classification of viruses into taxa, but is not responsible for the nomenclature for taxa members. International experts groups, such as the ICTV Study Groups, recommend the classification and naming of viruses and their strains, variants, and isolates. The ICTV Filoviridae Study Group has recently introduced an updated classification and nomenclature for filoviruses. Subsequently, and together with numerous other filovirus experts, a cons… Show more
“…Twenty-eight days postvaccination, animals were challenged with a lethal dose of mouse-adapted EBOV (ma-EBOV) (72). Although all control animals succumbed to EBOV infection by day 7, 100% protection was conferred by 4.0-μg and 40-μg Ebola MDNP prime-boost vaccinations, with no EBOV clinical pathological findings observed over the course of the study (Fig.…”
Section: Resultsmentioning
confidence: 99%
“…Mice were inoculated with a target titer of 1,000 pfu of ma-EBOV (72). All studies were conducted in the USAMRIID Biosafety Level 4 containment facility.…”
Vaccines have had broad medical impact, but existing vaccine technologies and production methods are limited in their ability to respond rapidly to evolving and emerging pathogens, or sudden outbreaks. Here, we develop a rapid-response, fully synthetic, single-dose, adjuvant-free dendrimer nanoparticle vaccine platform wherein antigens are encoded by encapsulated mRNA replicons. To our knowledge, this system is the first capable of generating protective immunity against a broad spectrum of lethal pathogen challenges, including H1N1 influenza, Toxoplasma gondii, and Ebola virus. The vaccine can be formed with multiple antigen-expressing replicons, and is capable of eliciting both CD8+ T-cell and antibody responses. The ability to generate viable, contaminant-free vaccines within days, to single or multiple antigens, may have broad utility for a range of diseases.
“…Twenty-eight days postvaccination, animals were challenged with a lethal dose of mouse-adapted EBOV (ma-EBOV) (72). Although all control animals succumbed to EBOV infection by day 7, 100% protection was conferred by 4.0-μg and 40-μg Ebola MDNP prime-boost vaccinations, with no EBOV clinical pathological findings observed over the course of the study (Fig.…”
Section: Resultsmentioning
confidence: 99%
“…Mice were inoculated with a target titer of 1,000 pfu of ma-EBOV (72). All studies were conducted in the USAMRIID Biosafety Level 4 containment facility.…”
Vaccines have had broad medical impact, but existing vaccine technologies and production methods are limited in their ability to respond rapidly to evolving and emerging pathogens, or sudden outbreaks. Here, we develop a rapid-response, fully synthetic, single-dose, adjuvant-free dendrimer nanoparticle vaccine platform wherein antigens are encoded by encapsulated mRNA replicons. To our knowledge, this system is the first capable of generating protective immunity against a broad spectrum of lethal pathogen challenges, including H1N1 influenza, Toxoplasma gondii, and Ebola virus. The vaccine can be formed with multiple antigen-expressing replicons, and is capable of eliciting both CD8+ T-cell and antibody responses. The ability to generate viable, contaminant-free vaccines within days, to single or multiple antigens, may have broad utility for a range of diseases.
“…The progenitor isolate used for the initial inoculations in guinea pigs was a stock preparation from the original clinical sample that had previously been passaged once in guinea pigs and twice on VeroE6 cells. This progenitor virus was designated Sudan virus/C.porcellus-lab/SSD/ 1976/Nzara-Boneface (SUDV-p), in accordance with established guidelines (14,15). The sequence is not identical to that of wild-type SUDV; thus, the viral sequence of SUDV-p has been deposited in GenBank.…”
Infections with Sudan virus (SUDV), a member of the genus Ebolavirus, result in a severe hemorrhagic fever with a fatal outcome in over 50% of human cases. The paucity of prophylactics and therapeutics against SUDV is attributed to the lack of a small-animal model to screen promising compounds. By repeatedly passaging SUDV within the livers and spleens of guinea pigs in vivo, a guinea pig-adapted SUDV variant (SUDV-GA) uniformly lethal to these animals, with a 50% lethal dose (LD 50 ) of 5.3 ؋ 10 ؊2 50% tissue culture infective doses (TCID 50 ), was developed. Animals infected with SUDV-GA developed high viremia and died between 9 and 14 days postinfection. Several hallmarks of SUDV infection, including lymphadenopathy, increased liver enzyme activities, and coagulation abnormalities, were observed. Virological analyses and gross pathology, histopathology, and immunohistochemistry findings indicate that SUDV-GA replicates in the livers and spleens of infected animals similarly to SUDV infections in nonhuman primates. These developments will accelerate the development of specific medical countermeasures in preparation for a future disease outbreak due to SUDV.
IMPORTANCE
A disease outbreak due to Ebola virus (EBOV), suspected to have emerged duringDecember 2013 in Guinea, with over 11,000 dead and 28,000 infected, is finally winding down. Experimental EBOV vaccines and treatments were administered to patients under compassionate circumstances with promising results, and availability of an approved countermeasure appears to be close. However, the same range of experimental candidates against a potential disease outbreak caused by other members of the genus Ebolavirus, such as Sudan virus (SUDV), is not readily available. One bottleneck contributing to this situation is the lack of a small-animal model to screen promising drugs in an efficient and economical manner. To address this, we have generated a SUDV variant (SUDV-GA) that is uniformly lethal to guinea pigs. Animals infected with SUDV-GA develop disease similar to that of SUDV-infected humans and monkeys. We believe that this model will significantly accelerate the development of lifesaving measures against SUDV infections.
“…Ebola virus (EBOV), Tai Forest virus (TAFV), Reston virus (RESTV), Sudan virus (SUDV), and Bundibugyo virus (BDBV) are the virus making up the Ebolavirus genus [10]. EBOV and SUDV come as the most frequent outbreak-causing virus which has the case-fatality rate of 76 and 55% (CI 95%), respectively [11].…”
Ebola is an acute disease causing hemorrhagic fever marked with high mortality rate. The patients who suffer from Ebola only receive palliative care because there is no available drug which can consistently cure this disease. To date, no cure has been found to treat this disease. Bioinformatics and computer-aided drug discovery and development (CADDD) are employed to utilize the readily available genomic and proteomic data and enhance the hit rate of the novel and repurposed drug for Ebola therapy. Additionally, the time and cost of wet laboratory experiments can be drastically reduced by the support of bioinformatics approach. Our laboratory has succeeded not only in creating the bioinformatics research pipeline but also screening and developing the drug candidate to cure Ebola. Through pharmacophore-based virtual screening and molecular docking simulations, we discovered that about three Indonesian natural product compounds have noteworthy molecular interactions against EBOV VP35 protein, which are responsible for the RNA synthesis of the Ebola. These compounds can be reevaluated further through advances in in silico simulation and in vitro experiments.
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