scholarly journals Experimental Assessment of Possible Factors Associated with Tick-Borne Encephalitis Vaccine Failure

2021 ◽  
Vol 9 (6) ◽  
pp. 1172
Author(s):  
Ksenia Tuchynskaya ◽  
Viktor Volok ◽  
Victoria Illarionova ◽  
Egor Okhezin ◽  
Alexandra Polienko ◽  
...  
Keyword(s):  
Vaccine Efficacy ◽  
Protective Efficacy ◽  
Viral Rna ◽  
Dependent Manner ◽  
Related Factors ◽  
Effective Measure ◽  
Challenge Virus ◽  
Tick Borne Encephalitis ◽  
Tbe Virus ◽  
The Brain

Currently the only effective measure against tick-borne encephalitis (TBE) is vaccination. Despite the high efficacy of approved vaccines against TBE, rare cases of vaccine failures are well documented. Both host- and virus-related factors can account for such failures. In this work, we studied the influence of mouse strain and sex and the effects of cyclophosphamide-induced immunosuppression on the efficacy of an inactivated TBE vaccine. We also investigated how an increased proportion of non-infectious particles in the challenge TBE virus would affect the protectivity of the vaccine. The vaccine efficacy was assessed by mortality, morbidity, levels of viral RNA in the brain of surviving mice, and neutralizing antibody (NAb) titers against the vaccine strain and the challenge virus. Two-dose vaccination protected most animals against TBE symptoms and death, and protectivity depended on strain and sex of mice. Immunosuppression decreased the vaccine efficacy in a dose-dependent manner and changed the vaccine-induced NAb spectrum. The vaccination protected mice against TBE virus neuroinvasion and persistence. However, viral RNA was detected in the brain of some asymptomatic animals at 21 and 42 dpi. Challenge with TBE virus enriched with non-infectious particles led to lower NAb titers in vaccinated mice after the challenge but did not affect the protective efficacy.

scholarly journals Virus-Like Particle Vaccine Confers Protection against a Lethal Newcastle Disease Virus Challenge in Chickens and Allows a Strategy of Differentiating Infected from Vaccinated Animals

2014 ◽  
Vol 21 (3) ◽  
pp. 360-365 ◽  
Author(s):  
Jae-Keun Park ◽  
Dong-Hun Lee ◽  
Seong-Su Yuk ◽  
Erdene-Ochir Tseren-Ochir ◽  
Jung-Hoon Kwon ◽  
...  
Keyword(s):  
Newcastle Disease Virus ◽  
Disease Virus ◽  
Newcastle Disease ◽  
Protective Efficacy ◽  
Expression System ◽  
Enzyme Linked Immunosorbent Assay ◽  
Dependent Manner ◽  
Lethal Challenge ◽  
Challenge Virus ◽  
Virus Challenge

ABSTRACTIn this study, we developed Newcastle disease virus (NDV) virus-like particles (VLPs) expressing NDV fusion (F) protein along with influenza virus matrix 1 (M1) protein using the insect cell expression system. Specific-pathogen-free chickens were immunized with oil emulsion NDV VLP vaccines containing increasing dosages of VLPs (0.4, 2, 10, or 50 μg of VLPs/0.5-ml dose). Three weeks after immunization, the immunogenicity of the NDV VLP vaccines was determined using a commercial enzyme-linked immunosorbent assay (ELISA) kit, and a lethal challenge using a highly virulent NDV strain was performed to evaluate the protective efficacy of the NDV VLP vaccines. NDV VLP vaccines elicited anti-NDV antibodies and provided protection against a lethal challenge in a dose-dependent manner. Although the VLP vaccines containing 0.4 and 2 μg of VLPs failed to achieve high levels of protection, a single immunization with NDV VLP vaccine containing 10 or 50 μg could fully protect chickens from a lethal challenge and greatly reduced challenge virus shedding. Furthermore, we could easily differentiate infected from vaccinated animals (DIVA) using the hemagglutination inhibition (HI) test. These results strongly suggest that utilization of NDV VLP vaccine in poultry species may be a promising strategy for the better control of NDV.

scholarly journals Effectiveness of Specific Prevention of Tick-Borne Encephalitis

2020 ◽  
Vol 20 (3) ◽  
pp. 174-186
Author(s):  
M. S. Shcherbinina ◽  
O. A. Barkhaleva ◽  
O. S. Dorokhova ◽  
A. A. Movsesyants
Keyword(s):  
Protective Efficacy ◽  
Real Life ◽  
Genetic Population ◽  
Long Term Study ◽  
Genetic Subtypes ◽  
Tick Borne Encephalitis ◽  
Tbe Virus ◽  
Promising Area ◽  
Protective Antibodies ◽  
The Stability

Vaccination remains the only way to prevent tick-borne encephalitis (TBE). All TBE vaccines are based on strains of the Far Eastern and European subtypes of TBE virus. Currently, the Siberian subtype of the virus, which differs from the vaccine strains, accounts for 80–100% of the genetic population of TBE virus in most of Russia. The proportion of TBE vaccinated patients among those infected was different from year to year in Russia, e.g. 3.9% in 2012 and 1.5% in 2018, there were also some fatal cases registered among vaccinated patients. In this regard, evaluation of the effectiveness of vaccination against various genetic subtypes of TBE is a promising area of research. The purpose of this study was to summarise the results of studies investigating effectiveness of specific prevention of TBE as regards various genetic subtypes of the virus. The paper analyses data on the effectiveness of TBE vaccination in experimental settings and in real life. It was demonstrated that the use of vaccines for prevention of TBE is effective, provided the vaccination coverage is not less than 80%. The paper cites the data from a long-term study of the stability and protective activity of vaccine immunity against TBE virus strains isolated in highly endemic territories. It was established that TBE vaccines have high immunogenic activity and contribute to the production of stable protective antibodies against the strains of the three genetic subtypes of the virus. Protective efficacy of vaccination depends on the number of vaccinations received, the vaccination scheme, gender and age of those vaccinated. The paper concludes by saying that further studies are needed to assess TBE vaccine efficacy in order to improve vaccination tactics, to better understand causes of morbidity and mortality among vaccinated individuals.

scholarly journals Plant-Produced N-glycosylated Ag85A Exhibits Enhanced Vaccine Efficacy Against Mycobacterium tuberculosis HN878 Through Balanced Multifunctional Th1 T Cell Immunity

Vaccines ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 189
Author(s):  
Hongmin Kim ◽  
Kee Woong Kwon ◽  
Jaehun Park ◽  
Hyangju Kang ◽  
Yongjik Lee ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Vaccine Efficacy ◽  
Protective Efficacy ◽  
Vaccine Antigen ◽  
Effective Vaccine ◽  
Host Immune System ◽  
Effective Measure ◽  
Cell Immunity ◽  
Ifn Γ

Tuberculosis (TB) is one of the deadliest infectious diseases worldwide and is caused by Mycobacterium tuberculosis (Mtb). An effective vaccine to prevent TB is considered the most cost-effective measure for controlling this disease. Many different vaccine antigen (Ag) candidates, including well-known and newly identified Ags, have been evaluated in clinical and preclinical studies. In this study, we took advantage of a plant system of protein expression using Nicotiana benthamiana to produce N-glycosylated antigen 85A (G-Ag85A), which is one of the most well-characterized vaccine Ag candidates in the field of TB vaccines, and compared its immunogenicity and vaccine efficacy with those of nonglycosylated Ag85A (NG-Ag85A) produced with an Escherichia coli system. Notably, G-Ag85A induced a more robust IFN-γ response than NG-Ag85A, which indicated that G-Ag85A is well recognized by the host immune system during Mtb infection. We subsequently compared the vaccine potential of G-Ag85A and NG-Ag85A by evaluating their immunological features and substantial protection efficacies. Interestingly, G-Ag85A yielded moderately enhanced long-term protective efficacy, as measured in terms of bacterial burden and lung inflammation. Strikingly, G-Ag85A-immunized mice showed a more balanced proportion of multifunctional Th1-biased immune responses with sustained IFN-γ response than did NG-Ag85A-immunized mice. Collectively, plant-derived G-Ag85A could induce protective and balanced Th1 responses and confer long-term protection against a hypervirulent Mtb Beijing strain infection, which indicated that plant-produced G-Ag85A might provide an excellent example for the production of an Mtb subunit vaccine Ag and could be an effective platform for the development of anti-TB vaccines.

TBE in Croatia

2020 ◽  
Keyword(s):  
Tick Species ◽  
Limited Data ◽  
Notifiable Disease ◽  
Genetic Characteristics ◽  
Central European ◽  
Tick Borne Encephalitis ◽  
Tbe Virus ◽  
Endemic Areas ◽  
European Subtype

Even though tick-borne encephalitis (TBE) has been a notifiable disease in Croatia since 2007, there are no or only limited data available on the occurring tick species in the endemic areas, on the prevalence of TBE virus (TBEV) in ticks, its distribution in Croatia, and its genetic characteristics. Reporting of human cases also is very scarce. The Central European subtype of virus (TBEV-EU) appears to be present in Croatia

TBE in Moldova

2019 ◽  
Author(s):  
Wilhelm Erber ◽  
Tamara Vuković Janković
Keyword(s):  
Reliable Data ◽  
Tick Borne Encephalitis ◽  
Tbe Virus

Although there are no reliable data on the number of tick-borne encephalitis (TBE) cases or the percentage of infected ticks, based on the geography and the presence of TBE virus (TBEV) in all neighboring countries, it must be assumed that TBEV is present anywhere in Moldova.

Serotonin elicits long-lasting enhancement of rhythmic respiratory activity in turtle brain stems in vitro

2001 ◽  
Vol 91 (6) ◽  
pp. 2703-2712 ◽  
Author(s):  
Stephen M. Johnson ◽  
Julia E. R. Wilkerson ◽  
Daniel R. Henderson ◽  
Michael R. Wenninger ◽  
Gordon S. Mitchell
Keyword(s):  
Brain Stem ◽  
Respiratory Activity ◽  
Dependent Manner ◽  
Frequency Increase ◽  
Burst Frequency ◽  
Bath Application ◽  
Burst Amplitude ◽  
Dose Dependent ◽  
The Brain

Brain stem preparations from adult turtles were used to determine how bath-applied serotonin (5-HT) alters respiration-related hypoglossal activity in a mature vertebrate. 5-HT (5–20 μM) reversibly decreased integrated burst amplitude by ∼45% ( P < 0.05); burst frequency decreased in a dose-dependent manner with 20 μM abolishing bursts in 9 of 13 preparations ( P < 0.05). These 5-HT-dependent effects were mimicked by application of a 5-HT1A agonist, but not a 5-HT1B agonist, and were abolished by the broad-spectrum 5-HT antagonist, methiothepin. During 5-HT (20 μM) washout, frequency rebounded to levels above the original baseline for 40 min ( P < 0.05) and remained above baseline for 2 h. A 5-HT3 antagonist (tropesitron) blocked the post-5-HT rebound and persistent frequency increase. A 5-HT3 agonist (phenylbiguanide) increased frequency during and after bath application ( P < 0.05). When phenylbiguanide was applied to the brain stem of brain stem/spinal cord preparations, there was a persistent frequency increase ( P < 0.05), but neither spinal-expiratory nor -inspiratory burst amplitude were altered. The 5-HT3receptor-dependent persistent frequency increase represents a unique model of plasticity in vertebrate rhythm generation.

scholarly journals UV-induced neuronal degeneration in the rat cerebral cortex

2021 ◽  
Author(s):  
Mariko Nakata ◽  
Masayuki Shimoda ◽  
Shinya Yamamoto
Keyword(s):  
Uv Irradiation ◽  
Neuronal Degeneration ◽  
Uv Light ◽  
Brain Lesion ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Heme Oxygenase 1 ◽  
Dependent Manner ◽  
Focal Brain Injury ◽  
The Brain ◽  
And Oxidative Stress

Abstract Irradiation with ultraviolet (UV) light on the cortical surface can induce a focal brain lesion (UV lesion) in rodents. In the present study, we investigated the process of establishing a UV lesion. Rats underwent UV irradiation (365 nm wavelength, 2.0 mWh) over the dura, and time-dependent changes in the cortical tissue were analyzed histologically. We found that the majority of neurons in the lesion started to degenerate within 24 hours and the rest disappeared within 5 days after irradiation. UV-induced neuronal degeneration progressed in a layer-dependent manner. Moreover, UV-induced terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) positivity and heme oxygenase-1 (HO-1) immunoreactivity were also detected. These findings suggest that UV irradiation in the brain can induce gradual neural degeneration and oxidative stress. Importantly, UV vulnerability may vary among cortical layers. UV-induced cell death may be due to apoptosis; however, there remains a possibility that UV-irradiated cells were degenerated via processes other than apoptosis. The UV lesion technique will not only assist in investigating brain function at a targeted site but may also serve as a pathophysiological model of focal brain injury and/or neurodegenerative disorders.

scholarly journals pH-responsive antibodies for therapeutic applications

2021 ◽  
Vol 28 (1) ◽  
Author(s):  
Tomasz Klaus ◽  
Sameer Deshmukh
Keyword(s):  
Drug Delivery ◽  
Treatment Outcome ◽  
Tumor Microenvironment ◽  
Dependent Manner ◽  
Therapeutic Antibodies ◽  
Ph Responsive ◽  
Biologic Drugs ◽  
Car T ◽  
Ph Dependent ◽  
The Brain

AbstractTherapeutic antibodies are instrumental in improving the treatment outcome for certain disease conditions. However, to enhance their efficacy and specificity, many efforts are continuously made. One of the approaches that are increasingly explored in this field are pH-responsive antibodies capable of binding target antigens in a pH-dependent manner. We reviewed suitability and examples of these antibodies that are functionally modulated by the tumor microenvironment. Provided in this review is an update about antigens targeted by pH-responsive, sweeping, and recycling antibodies. Applicability of the pH-responsive antibodies in the engineering of chimeric antigen receptor T-cells (CAR-T) and in improving drug delivery to the brain by the enhanced crossing of the blood–brain barrier is also discussed. The pH-responsive antibodies possess strong treatment potential. They emerge as next-generation programmable engineered biologic drugs that are active only within the targeted biological space. Thus, they are valuable in targeting acidified tumor microenvironment because of improved spatial persistence and reduced on-target off-tumor toxicities. We predict that the programmable pH-dependent antibodies become powerful tools in therapies of cancer.

scholarly journals Quercetin Attenuates Brain Oxidative Alterations Induced by Iron Oxide Nanoparticles in Rats

2021 ◽  
Vol 22 (8) ◽  
pp. 3829
Author(s):  
Mohamed F. Dora ◽  
Nabil M. Taha ◽  
Mohamed A. Lebda ◽  
Aml E. Hashem ◽  
Mohamed S. Elfeky ◽  
...  
Keyword(s):  
Iron Oxide ◽  
B Cell Lymphoma ◽  
Basal Diet ◽  
Protective Role ◽  
Iron Oxide Nanoparticle ◽  
Albino Rats ◽  
Peroxisome Proliferator ◽  
Dependent Manner ◽  
Peroxisome Proliferator Activated Receptor ◽  
The Brain

Iron oxide nanoparticle (IONP) therapy has diverse health benefits but high doses or prolonged therapy might induce oxidative cellular injuries especially in the brain. Therefore, we conducted the current study to investigate the protective role of quercetin supplementation against the oxidative alterations induced in the brains of rats due to IONPs. Forty adult male albino rats were allocated into equal five groups; the control received a normal basal diet, the IONP group was intraperitoneally injected with IONPs of 50 mg/kg body weight (B.W.) and quercetin-treated groups had IONPs + Q25, IONPs + Q50 and IONPs + Q100 that were orally supplanted with quercetin by doses of 25, 50 and 100 mg quercetin/kg B.W. daily, respectively, administrated with the same dose of IONPs for 30 days. IONPs induced significant increases in malondialdehyde (MDA) and significantly decreased reduced glutathione (GSH) and oxidized glutathione (GSSG). Consequently, IONPs significantly induced severe brain tissue injuries due to the iron deposition leading to oxidative alterations with significant increases in brain creatine phosphokinase (CPK) and acetylcholinesterase (AChE). Furthermore, IONPs induced significant reductions in brain epinephrine, serotonin and melatonin with the downregulation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and mitochondrial transcription factor A (mtTFA) mRNA expressions. IONPs induced apoptosis in the brain monitored by increases in caspase 3 and decreases in B-cell lymphoma 2 (Bcl2) expression levels. Quercetin supplementation notably defeated brain oxidative damages and in a dose-dependent manner. Therefore, quercetin supplementation during IONPs is highly recommended to gain the benefits of IONPs with fewer health hazards.

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