Результаты поиска

A Monovalent and Trivalent MVA-Based Vaccine Completely Protects Mice Against Lethal Venezuelan, Western, and Eastern Equine Encephalitis Virus Aerosol Challenge.

Venezuelan, eastern and western equine encephalitis viruses (EEV) can cause severe disease of the central nervous system in humans, potentially leading to permanent damage or death. Yet, no licensed vaccine for human use is available to protect against these mosquito-borne pathogens, which can be aerosolized and therefore pose a bioterror threat in addition to the risk of natural outbreaks. Using the mouse aerosol challenge model, we evaluated the immunogenicity and efficacy of EEV vaccines that are based on the modified vaccinia Ankara-Bavarian Nordic (MVA-BN®) vaccine platform: three monoval

Novel DNA-launched Venezuelan equine encephalitis virus vaccine with rearranged genome.

Novel live-attenuated V4020 vaccine was prepared for Venezuelan equine encephalitis virus (VEEV), an alphavirus from the Togaviridae family. The genome of V4020 virus was rearranged, with the capsid gene expressed using a duplicate subgenomic promoter downstream from the glycoprotein genes. V4020 also included both attenuating mutations from the TC83 VEEV vaccine secured by mutagenesis to prevent reversion mutations. The full-length infectious RNA of V4020 vaccine virus was expressed from pMG4020 plasmid downstream from the CMV promoter and launched replication of live-attenuated V4020 in vitr

Novel indole-2-carboxamide compounds are potent broad-spectrum antivirals active against western equine encephalitis virus in vivo.

Neurotropic alphaviruses, including western, eastern, and Venezuelan equine encephalitis viruses, cause serious and potentially fatal central nervous system infections in humans for which no currently approved therapies exist. We previously identified a series of thieno[3,2-b]pyrrole derivatives as novel inhibitors of neurotropic alphavirus replication, using a cell-based phenotypic assay (W. Peng et al., J. Infect. Dis. 199:950-957, 2009, doi:http://dx.doi.org/10.1086/597275), and subsequently developed second- and third-generation indole-2-carboxamide derivatives with improved potency, solub

Highly activated cytotoxic CD8 T cells express protective IL-10 at the peak of coronavirus-induced encephalitis.

Acute viral encephalitis requires rapid pathogen elimination without significant bystander tissue damage. In this article, we show that IL-10, a potent anti-inflammatory cytokine, is produced transiently at the peak of infection by CD8 T cells in the brains of coronavirus-infected mice. IL-10(+)CD8 and IL-10(-)CD8 T cells interconvert during acute disease, possibly based on recent Ag exposure. Strikingly, IL-10(+)CD8 T cells were more highly activated and cytolytic than IL-10(-)CD8 T cells, expressing greater levels of proinflammatory cytokines and chemokines, as well as cytotoxic proteins. Ev

Posterior reversible encephalopathy syndrome following measles vaccination.

Due to recent domestic measles outbreaks in Japan, the Japanese government has mandated measles vaccination at ages 14 and 17 since April 2008. Since then, the number of people receiving measles vaccination has increased in Japan. Measles vaccination may cause serious neurological complications including encephalopathy, although the incidence is very low. We report here an adult case of posterior reversible encephalopathy syndrome (PRES) and myeloradiculoneuropathy following measles vaccination. Brain MRI demonstrated typical findings of PRES, high intensity signals in the occipital lobes on F

Телеметрический анализ для обнаружения фебрильных реакций у мышей после вакцинации живой вирусной вакциной.

Нечеловеческие приматы (НВП) считаются наиболее подходящей моделью для прогнозирования того, как люди будут реагировать на многие инфекционные заболевания. С учетом этических и денежно-кредитных соображений, связанных с использованием НЖП, целесообразно использовать модели грызунов, которые являются прогнозирующими ответными мерами, которые, вероятно, будут наблюдаться у получателей вакцины. С помощью имплантированных средств телеметрии температура и активность тела отслеживались с помощью врожденных и изверженных штаммов мыши после введения живой вакцины против венесуэльского энцефалита (VEV)

DNA vaccines for biodefense.

An ideal biodefense vaccine platform would allow for the quick formulation of novel vaccines in response to emerging or engineered pathogens. The resultant vaccine should elicit protective immune responses in one to three doses and be unaffected by pre-existing immunity to vaccine components. In addition, it should be amenable to combination and multi-agent formulation, and should be safe for all populations and the environment. DNA vaccines can potentially meet all of these requirements; thus, this platform is being tested with several biodefense threats. Here, we provide a review of the curr

Защита хомяков венесуэльским вирусом энцефалита V3526 от смертельного воздействия укуса комаров и внутриперитональной инъекции.

В попытке усовершенствовать нынешнюю вакцину (TC-83) для вируса экин энцефалита (VEV) венесуэльского энцефалита (VEV) конкретные мутации, связанные со смягчением VEV в моделях грызунов, были вставлены в клон кДNA на полную длину осла Тринидадского осла штамма VEEV мутагенезом, ориентированным на объект. Поскольку, согласно сообщениям, некоторые вирусы являются более патогенными, когда они вводятся в результате укуса комара, чем тот же вирус, введенный в результате иглы, высказывались опасения по поводу того, что наличие слюны комаров или изменения в вирусе, вызванные копированием в комаре, мог

Venezuelan equine encephalitis virus vaccine candidate (V3526) safety, immunogenicity and efficacy in horses.

A new vaccine, V3526, is a live-attenuated virus derived by site-directed mutagenesis from a virulent clone of the Venezuelan equine encephalitis virus (VEEV) IA/B Trinidad donkey (TrD) strain, intended for human use in protection against Venezuelan equine encephalitis (VEE). Two studies were conducted in horses to evaluate the safety, immunogenicity, ability to boost and protective efficacy of V3526 against challenges of TrD and VEEV IE 64A99. Horses were vaccinated subcutaneously (SC) with 10(7), 10(5), 10(3) or 10(2) plaque-forming units (pfu) of V3526. Control horses were sham immunized. I

Increased post-traumatic survival of neurons in IL-6-knockout mice on a background of EAE susceptibility.

Axonal injury initiates a process of neuronal degeneration, with resulting death of neuronal cell bodies. We show here that in C57BL/6J mice, previously shown to have a limited ability to manifest a post-traumatic protective immunity, the rate of neuronal survival is increased if IL-6 is deficient during the first 24 hours after optic nerve injury. Immunocytochemical staining preformed 7 days after the injury revealed an increased number of activated microglia in the IL-6-deficient mice compared to the wild-type mice. In addition, IL-6-deficient mice showed an increased resistance to glutamate

Role of interferon and interferon regulatory factors in early protection against Venezuelan equine encephalitis virus infection.

To investigate the role of type I interferon (IFN) and its regulatory transacting proteins, interferon regulatory factors (IRF-1 and IRF-2), in early protection against infection with virulent Venezuelan equine encephalitis virus (VEE), we utilized mice with targeted mutations in the IFN-alpha/beta receptor, IRF-1, or IRF-2 genes. IFN-alpha/beta-receptor knockout mice are highly susceptible to peripheral infection with virulent or attenuated VEE, resulting in their death within 24 and 48 h, respectively. Treatment of normal macrophages with anti-IFN-alpha/beta antibody prior to and during infe

[Isolated abducens paralysis--a retrospective study of 165 patients].

In this retrospective study the case reports of 165 patients suffering from an abducens nerve palsy as the main presenting symptom were evaluated. The sixth nerve palsy was more frequent on the left (52%) than on the right hand side (38%), in 10% there was bilateral involvement. In 49 cases a vascular origin was suspected (29.7%), with diabetes mellitus as the most important risk factor (n = 35). Abducens palsies in inflammatory diseases (n = 32, 19.4%) were seen most often in multiple sclerosis (n = 11), viral meningoencephalitis (n = 5) and accompanying systemic viral infections (n = 5). Pos

Cardiopulmonary Exercise Testing Reveals Functional Limitations and Work Disability in Severe Post-COVID-19 and ME/CFS Patients.

BACKGROUND: Patients severely affected by post-COVID-19 condition (PCC) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) often experience long-term work incapacity, contributing to a growing economic burden. Organ-centered clinical diagnostics frequently fail to explain their work disability. OBJECTIVES: We aimed to objectively assess physical work ability using cardiopulmonary exercise testing (CPET) in a cohort of long-standing and severely affected PCC patients. We hypothesized: (1) patients with ME/CFS exhibit lower peak oxygen uptake (VO₂peak [mL/min/kg]) and peak power ou…

Противоположные агенты на основе гадолиния (Grigger Gadoliium Accumulation in the Hippocampus in Vivo и Mitochondial Alterations in Cheromotypic Hippocampal Tissual Cultures ex Vivo.

ПРИ Множестве склероза (MS) митохондриальная дисфункция способствует прогрессированию заболеваний и может негативно сказаться на когнитивной функции, особенно в таких уязвимых регионах, как гиппокамп. Гадолиниевы контрастные агенты (GBCA) широко используются для диагностирования MS на основе изображений; однако, как показывают данные, гадолиний (Gd) может высвобождаться из низкостабильных агентов и сохраняться в мозге. Остается неясным, влияет ли сохранение Gd на нейронную митохондрию, особенно в условиях провокации. Мы изучили сохранение гиппокампального Gd после воздействия в Vivo GBCA и про

Совпадение в аннотации оригинала
BACKGROUND: In multiple sclerosis (MS), mitochondrial dysfunction contributes to disease progression and may impair cognitive function, part … ed mitochondrial effects in hippocampal slice cultures. METHODS: Mice with experimental autoimmune encephalomyelitis (EAE) and healthy controls received repeated injections of linear gadopentetate-dimeglumine (gadopentetate) or macrocyclic gadobutrol (cumulative dose: 20 mmol/kg body weight). Hippocampal Gd distribution and retention kinetics were analyzed 1, 10, …