scholarly journals Mutations in the A34R gene increase the immunogenicity of vaccinia virus

2021 ◽  
Vol 25 (2) ◽  
pp. 139-146
Author(s):  
S. N. Shchelkunov ◽  
T. V. Bauer ◽  
S. N. Yakubitskiy ◽  
A. A. Sergeev ◽  
A. S. Kabanov ◽  
...  
Keyword(s):  
Vaccinia Virus ◽  
Point Mutations ◽  
World Health ◽  
Smallpox Vaccination ◽  
Virus Infections ◽  
Pathogenic Viruses ◽  
Foreign Genes ◽  
Health Organization ◽  
Human Infections

Vaccination is the most simple and reliable approach of protection to virus infections. The most effective agents are live vaccines, usually low-virulence organisms for humans and closely related to pathogenic viruses or attenuated as a result of mutations/deletions in the genome of pathogenic virus. Smallpox vaccination with live vaccinia virus (VACV) closely related to smallpox virus played a key role in the success of the global smallpox eradication program carried out under the World Health Organization auspices. As a result of the WHO decision as of 1980 to stop smallpox vaccination, humankind has lost immunity not only to smallpox, but also to other zoonotic, orthopoxviruscaused human infections. This new situation allows orthopoxviruses to circulate in the human population and, as a consequence, to alter several established concepts of the ecology and range of sensitive hosts for various orthopoxvirus species. Classic VACV-based live vaccine for vaccination against orthopoxvirus infections is out of the question, because it can cause severe side effects. Therefore, the development of new safe vaccines against orthopoxviral infections of humans and animals is an important problem. VACV attenuation by modern approaches carried out by targeted inactivation of certain virus genes and usually leads to a decrease in the effectiveness of VACV in vivo propagation. As a result, it can cause a diminishing of the immune response after administration of attenuated virus to patients at standard doses. The gene for thymidine kinase is frequently used for insertion/inactivation of foreign genes and it causes virus attenuation. In this research, the effect of the introduction of two point mutations into the A34R gene of attenuated strain LIVP-GFP (ТК–), which increase the yield of extracellular enveloped virions (EEV), on the pathogenicity and immunogenicity of VACV LIVP-GFP-A34R administered intranasally to laboratory mice were studied. It was shown that increase in EEV production by recombinant strain VACV LIVP-GFP-A34R does not change the attenuated phenotype characteristic of the parental strain LIVP-GFP, but causes a significantly larger production of VACV-specific antibodies.

scholarly journals Enhancing the Protective Immune Response to Administration of a LIVP-GFP Live Attenuated Vaccinia Virus to Mice

Pathogens ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 377
Author(s):  
Sergei N. Shchelkunov ◽  
Stanislav N. Yakubitskiy ◽  
Kseniya A. Titova ◽  
Stepan A. Pyankov ◽  
Alexander A. Sergeev
Keyword(s):  
Genetic Engineering ◽  
Vaccinia Virus ◽  
Fluorescent Protein ◽  
Point Mutations ◽  
Protein Product ◽  
Smallpox Vaccination ◽  
Green Fluorescent Protein Gene ◽  
Kinase Gene ◽  
Foreign Genes ◽  
Green Fluorescent

Following the WHO announcement of smallpox eradication, discontinuation of smallpox vaccination with vaccinia virus (VACV) was recommended. However, interest in VACV was soon renewed due to the opportunity of genetic engineering of the viral genome by directed insertion of foreign genes or introduction of mutations or deletions into selected viral genes. This genomic technology enabled production of stable attenuated VACV strains producing antigens of various infectious agents. Due to an increasing threat of human orthopoxvirus re-emergence, the development of safe highly immunogenic live orthopoxvirus vaccines using genetic engineering methods has been the challenge in recent years. In this study, we investigated an attenuated VACV LIVP-GFP (TK-) strain having an insertion of the green fluorescent protein gene into the viral thymidine kinase gene, which was generated on the basis of the LIVP (Lister-Institute for Viral Preparations) strain used in Russia as the first generation smallpox vaccine. We studied the effect of A34R gene modification and A35R gene deletion on the immunogenic and protective properties of the LIVP-GFP strain. The obtained data demonstrate that intradermal inoculation of the studied viruses induces higher production of VACV-specific antibodies compared to their levels after intranasal administration. Introduction of two point mutations into the A34R gene, which increase the yield of extracellular enveloped virions, and deletion of the A35R gene, the protein product of which inhibits presentation of antigens by MHC II, enhances protective potency of the created LIVP-TK--A34R*-dA35R virus against secondary lethal orthopoxvirus infection of BALB/c mice even at an intradermal dose as low as 103 plaque forming units (PFU)/mouse. This virus may be considered not only as a candidate attenuated live vaccine against smallpox and other human orthopoxvirus infections but also as a vector platform for development of safe multivalent live vaccines against other infectious diseases using genetic engineering methods.

scholarly journals Influenza update: no new animal H5N1 infections reported in European Union this week, and animal and human infections continue to be reported elsewhere

2006 ◽  
Vol 11 (16) ◽  
Author(s):  
Collective Editorial team
Keyword(s):  
European Union ◽  
Influenza Virus ◽  
World Health ◽  
Virus Infections ◽  
H5n1 Avian Influenza Virus ◽  
H5n1 Avian Influenza ◽  
The World ◽  
Health Organization ◽  
Human Infections ◽  
Human H5n1

The global cumulative total of human H5N1 avian influenza virus infections reported to and confirmed by the World Health Organization (WHO) since 2003 is 196

Antimicrobial peptides for the treatment of pulmonary tuberculosis, allies or foes?

2018 ◽  
Vol 24 (10) ◽  
pp. 1138-1147
Author(s):  
Bruno Rivas-Santiago ◽  
Flor Torres-Juarez
Keyword(s):  
Pulmonary Tuberculosis ◽  
Antimicrobial Peptides ◽  
Experimental Models ◽  
New Drugs ◽  
World Health ◽  
Public Health Issue ◽  
Health Organization ◽  
Drug Resistant Strains

Tuberculosis is an ancient disease that has become a serious public health issue in recent years, although increasing incidence has been controlled, deaths caused by Mycobacterium tuberculosis have been accentuated due to the emerging of multi-drug resistant strains and the comorbidity with diabetes mellitus and HIV. This situation is threatening the goals of World Health Organization (WHO) to eradicate tuberculosis in 2035. WHO has called for the creation of new drugs as an alternative for the treatment of pulmonary tuberculosis, among the plausible molecules that can be used are the Antimicrobial Peptides (AMPs). These peptides have demonstrated remarkable efficacy to kill mycobacteria in vitro and in vivo in experimental models, nevertheless, these peptides not only have antimicrobial activity but also have a wide variety of functions such as angiogenesis, wound healing, immunomodulation and other well-described roles into the human physiology. Therapeutic strategies for tuberculosis using AMPs must be well thought prior to their clinical use; evaluating comorbidities, family history and risk factors to other diseases, since the wide function of AMPs, they could lead to collateral undesirable effects.

scholarly journals Targeting CD146 with a 64Cu-labeled antibody enables in vivo immunoPET imaging of high-grade gliomas

2015 ◽  
Vol 112 (47) ◽  
pp. E6525-E6534 ◽  
Author(s):  
Yunan Yang ◽  
Reinier Hernandez ◽  
Jun Rao ◽  
Li Yin ◽  
Yazhuo Qu ◽  
...  
Keyword(s):  
Tumor Grade ◽  
The Cancer Genome Atlas ◽  
World Health ◽  
Positive Staining ◽  
Therapeutic Effects ◽  
Clinical Value ◽  
Positron Emission ◽  
Resected Tumor ◽  
Health Organization

Given the highly heterogeneous character of brain malignancies and the associated implication for its proper diagnosis and treatment, finding biomarkers that better characterize this disease from a molecular standpoint is imperative. In this study, we evaluated CD146 as a potential molecular target for diagnosis and targeted therapy of glioblastoma multiforme (GBM), the most common and lethal brain malignancy. YY146, an anti-CD146 monoclonal antibody, was generated and radiolabeled for noninvasive positron-emission tomography (PET) imaging of orthotopic GBM models. 64Cu-labeled YY146 preferentially accumulated in the tumors of mice bearing U87MG xenografts, which allowed the acquisition of high-contrast PET images of small tumor nodules (∼2 mm). Additionally, we found that tumor uptake correlated with the levels of CD146 expression in a highly specific manner. We also explored the potential therapeutic effects of YY146 on the cancer stem cell (CSC) and epithelial-to-mesenchymal (EMT) properties of U87MG cells, demonstrating that YY146 can mitigate those aggressive phenotypes. Using YY146 as the primary antibody, we performed histological studies of World Health Organization (WHO) grades I through IV primary gliomas. The positive correlation found between CD146-positive staining and high tumor grade (χ2 = 9.028; P = 0.029) concurred with the GBM data available in The Cancer Genome Atlas (TCGA) and validated the clinical value of YY146. In addition, we demonstrate that YY146 can be used to detect CD146 in various cancer cell lines and human resected tumor tissues of multiple other tumor types (gastric, ovarian, liver, and lung), indicating a broad applicability of YY146 in solid tumors.

scholarly journals Death of the King: The Introduction of Vaccination into Nepal in 1816

2018 ◽  
Vol 63 (1) ◽  
pp. 24-43 ◽  
Author(s):  
Susan Heydon
Keyword(s):  
Communicable Disease ◽  
World Health ◽  
Smallpox Vaccination ◽  
Communicable Disease Control ◽  
Eradication Programme ◽  
Early Appearance ◽  
Colonial Authority ◽  
History Of ◽  
Global Eradication ◽  
Health Organization

This article explores the introduction of smallpox vaccination into Nepal in 1816 at the request of the Nepalese government; the king, however, was not vaccinated, contracted the disease and died. British hopes that vaccination would be extended throughout the country did not eventuate. The article examines the significance of this early appearance of vaccination in Nepal for both Nepalese and British, and relates it to the longer history of smallpox control and eventual eradication. When the Nepalese requested World Health Organization (WHO) assistance with communicable disease control in the mid-twentieth century little had changed for most Nepalese. We know about the events in 1816 through the letters of the newly imposed British Resident after Nepal’s military defeat in the Anglo-Nepal War (1814–16). By also drawing on other sources and foregrounding Nepal, it becomes possible to build up a more extensive picture of smallpox in Nepal that shows not only boundaries and limits to colonial authority and influence but also how governments may adopt and use technologies on their own terms and for their own purposes. Linking 1816 to the ultimately successful global eradication programme 150 years later reminds us of the need to think longer term as to why policies and programmes may or may not work as planned.

scholarly journals Virtual Screening and Statistical Analysis in the Design of New Caffeine Analogues Molecules with Potential Epithelial Anticancer Activity

2018 ◽  
Vol 24 (5) ◽  
pp. 576-594 ◽  
Author(s):  
Josivan da Silva Costa ◽  
Karina da Silva Lopes Costa ◽  
Josiane Viana Cruz ◽  
Ryan da Silva Ramos ◽  
Luciane Barros Silva ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Binding Free Energy ◽  
Inhibitory Effect ◽  
Parametric Models ◽  
World Health ◽  
Pharmacokinetic Properties ◽  
Clinically Significant ◽  
Health Organization

About 132 thousand cases of melanoma (more severe type of skin cancer) were registered in 2014 according to the World Health Organization. This type of cancer significantly affects the quality of life of individuals. Caffeine has shown potential inhibitory effect against epithelial cancer. In this study, it was proposed to obtain new caffeine-based molecules with potential epithelial anticancer activity. For this, a training set of 21 molecules was used for pharmacophore perception procedures. Multiple linear regression analyses were used to propose mono-, bi-, tri-, and tetra-parametric models applied in the prediction of the activity. The generated pharmacophore was used to select 350 molecules available at the ZINCpharmer server, followed by reduction to 24 molecules, after selection using the Tanimoto index, yielding 10 molecules after final selection by predicted activity values > 1.5229. These ten molecules had better pharmacokinetic properties than the other ones used as reference and within the clinically significant limits. Only two molecules show minor hits of toxicity and were submitted to molecular docking procedures, showing BFE (binding free energy) values lower than the reference values. Statistical analyses indicated strong negative correlations between BFE and pharmacophoric properties (high influence on BFE lowering) and practically null correlation between BFE and BBB. The two most promising molecules can be indicated as candidates for further in vitro and in vivo analyzes.

scholarly journals Novel Antiviral Activities of Obatoclax, Emetine, Niclosamide, Brequinar, and Homoharringtonine

2019 ◽  
Author(s):  
Petter I. Andersen ◽  
Klara Krpina ◽  
Aleksandr Ianevski ◽  
Nastassia Shtaida ◽  
Eunji Jo ◽  
...  
Keyword(s):  
Influenza A ◽  
Rift Valley Fever Virus ◽  
Antiviral Agents ◽  
Viral Disease ◽  
World Health ◽  
Valley Fever ◽  
The World ◽  
Health Organization ◽  
Hiv 1

Viruses are the major causes of acute and chronic infectious diseases in the world. According to the World Health Organization, there is an urgent need for better control of viral diseases. Re-purposing existing antiviral agents from one viral disease to another could play a pivotal role in this process. Here we identified novel activities of obatoclax and emetine against herpes simplex virus type 2 (HSV-2), human immunodeficiency virus 1 (HIV-1), echovirus 1 (EV1), human metapneumovirus (HMPV) and Rift Valley fever virus (RVFV) in cell cultures. Moreover, we demonstrated novel activities of emetine against influenza A virus (FluAV), niclosamide against HSV-2, brequinar against HIV-1, and homoharringtonine against EV1. Our findings may expand the spectrum of indications of these safe-in-man agents and reinforce the arsenal of available antiviral therapeutics pending the results of further in vivo tests.

scholarly journals Therapeutic Effectiveness and Safety of Repurposing Drugs for the Treatment of COVID-19: Position Standing in 2021

2021 ◽  
Vol 12 ◽  
Author(s):  
Safaet Alam ◽  
Taslima Binte Kamal ◽  
Md. Moklesur Rahman Sarker ◽  
Jin-Rong Zhou ◽  
S. M. Abdur Rahman ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Case Series ◽  
Basic Knowledge ◽  
World Health ◽  
Current Status ◽  
Drug Candidates ◽  
Health Organization ◽  
Meta Analyses

COVID-19, transmitted by SARS-CoV-2, is one of the most serious pandemic situations in the history of mankind, and has already infected a huge population across the globe. This horrendously contagious viral outbreak was first identified in China and within a very short time it affected the world's health, transport, economic, and academic sectors. Despite the recent approval of a few anti-COVID-19 vaccines, their unavailability and insufficiency along with the lack of other potential therapeutic options are continuing to worsen the situation, with valuable lives continuing to be lost. In this situation, researchers across the globe are focusing on repurposing prospective drugs and prophylaxis such as favipiravir, remdesivir, chloroquine, hydroxychloroquine, ivermectin, lopinavir-ritonavir, azithromycin, doxycycline, ACEIs/ARBs, rivaroxaban, and protease inhibitors, which were preliminarily based on in vitro and in vivo pharmacological and toxicological study reports followed by clinical applications. Based on available preliminary data derived from limited clinical trials, the US National Institute of Health (NIH) and USFDA also recommended a few drugs to be repurposed i.e., hydroxychloroquine, remdesivir, and favipiravir. However, World Health Organization later recommended against the use of chloroquine, hydroxychloroquine, remdesivir, and lopinavir/ritonavir in the treatment of COVID-19 infections. Combining basic knowledge of viral pathogenesis and pharmacodynamics of drug molecules as well as in silico approaches, many drug candidates have been investigated in clinical trials, some of which have been proven to be partially effective against COVID-19, and many of the other drugs are currently under extensive screening. The repurposing of prospective drug candidates from different stages of evaluation can be a handy wellspring in COVID-19 management and treatment along with approved anti-COVID-19 vaccines. This review article combined the information from completed clinical trials, case series, cohort studies, meta-analyses, and retrospective studies to focus on the current status of repurposing drugs in 2021.

scholarly journals Suppression of p53-inducible gene 3 is significant for glioblastoma progression and predicts poor patient prognosis

Tumor Biology ◽  
2017 ◽  
Vol 39 (3) ◽  
pp. 101042831769457 ◽  
Author(s):  
Jishu Quan ◽  
Yong Li ◽  
Meihua Jin ◽  
Dunfu Chen ◽  
Xuezhe Yin ◽  
...  
Keyword(s):  
Cox Regression ◽  
Good Prognosis ◽  
World Health ◽  
Loss Of Function ◽  
Cox Regression Analysis ◽  
Normal Tissues ◽  
Health Organization ◽  
Proliferation And Invasion ◽  
Inducible Gene

Glioblastoma is the most malignant and invasive brain tumor with extremely poor prognosis. p53-inducible gene 3, a downstream molecule of the tumor suppressor p53, has been found involved in apoptosis and oxidative stress response. However, the functions of p53-inducible gene 3(PIG3) in cancer are far from clear including glioblastoma. In this study, we found that p53-inducible gene 3 expression was suppressed in glioblastoma tissues compared with normal tissues. And the expression of p53-inducible gene 3 was significantly associated with the World Health Organization grade. Patients with high p53-inducible gene 3 expression have a significantly longer median survival time (15 months) than those with low p53-inducible gene 3 expression (8 months). According to Cox regression analysis, p53-inducible gene 3 was an independent prognostic factor with multivariate hazard ratio of 0.578 (95% confidence interval, 0.352–0.947; p = 0.030) for overall survival. Additionally, gain and loss of function experiments showed that knockdown of p53-inducible gene 3 significantly increased the proliferation and invasion ability of glioblastoma cells while overexpression of p53-inducible gene 3 inhibited the proliferation and invasion ability. The results of in vivo glioblastoma models further confirmed that p53-inducible gene 3 suppression promoted glioblastoma progression. Altogether, our data suggest that high expression of p53-inducible gene 3 is significant for glioblastoma inhibition and p53-inducible gene 3 independently indicates good prognosis in patients, which might be a novel prognostic biomarker or potential therapeutic target in glioblastoma.

scholarly journals Quarantine for Zika Virus? Where is the Science?

2016 ◽  
Vol 10 (5) ◽  
pp. 704-706 ◽  
Author(s):  
Kristi L. Koenig
Keyword(s):  
Public Health ◽  
Zika Virus ◽  
Ebola Virus ◽  
Virus Disease ◽  
Rapid Test ◽  
Signs And Symptoms ◽  
World Health ◽  
Virus Infections ◽  
Health Organization ◽  
Spread Of Infection

AbstractIn January 2016, the World Health Organization warned that Zika virus is “spreading explosively” in the Americas and that up to 4 million infections could be present worldwide within a year. Soon thereafter, some politicians and authors publicly advocated for quarantine of travelers returning from regions where mosquitoes carrying Zika virus are prevalent. The public health tool of quarantine can be used to prevent the spread of infection by restricting the movement of persons who have been exposed to a deadly disease that can be transmitted from person to person before symptom onset. With 80% of Zika virus infections being asymptomatic, no rapid test being available to detect the virus, and primary transmission being via the bites of certain mosquitoes, application of quarantine in this setting is not scientifically sound or practically feasible. Rather, public health interventions should focus on preventing bites from infected mosquitoes, counseling pregnant women on the risks of fetal microcephaly and other birth defects, and identifying patients with signs and symptoms of Guillain-Barré syndrome. As was seen in the Ebola virus disease outbreak of 2014, non-evidence-based factors can influence policy decisions. Public health experts must ensure that policy makers are informed that quarantine is not a scientifically sound approach for the control of Zika virus. (Disaster Med Public Health Preparedness. 2016;0:1–3)

Sign in / Sign up

Export Citation Format

Share Document