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Incorporation of conserved nucleoprotein into influenza virus-like particles could provoke a broad protective immune response in BALB/c mice and chickens.

We engineered influenza A/goose/GD/1996 (H5N1) (clade 0) virus-like particles (VLPs) by coinfecting Sf9 cells with triple/quadruple recombinant baculovirus that expressed hemagglutinin (HA), neuraminidase (NA), and matrix 1 (M1) with or without nucleoprotein (NP). VLP3 (HA, NA, and M1) and VLP4 (HA, NA, M1, and NP) vaccines (containing 1 μg HA) with oil emulsion were administered to mice and chickens by intramuscular injection, and the immune responses were analyzed. The VLP-vaccinated mice demonstrated high antigen specific antibody titers and effective cellular immune responses. The mice and

A Novel Live Pichinde Virus-Based Vaccine Vector Induces Enhanced Humoral and Cellular Immunity after a Booster Dose.

UNLABELLED: Pichinde virus (PICV) is a bisegmented enveloped RNA virus that targets macrophages and dendritic cells (DCs) early in infection and induces strong innate and adaptive immunity in mice. We have developed a reverse genetics system to produce live recombinant PICV (strain P18) with a trisegmented RNA genome (rP18tri), which encodes all four PICV gene products and as many as two foreign genes. We have engineered the vector to express the green fluorescent protein (GFP) reporter gene (abbreviated as G in virus designations) and either the hemagglutination (HA [H]) or the nucleoprotein

A two-adjuvant multiantigen candidate vaccine induces superior protective immune responses against SARS-CoV-2 challenge.

An ideal vaccine against SARS-CoV-2 is expected to elicit broad immunity to prevent viral infection and disease, with efficient viral clearance in the upper respiratory tract (URT). Here, the N protein and prefusion-full S protein (SFLmut) are combined with flagellin (KF) and cyclic GMP-AMP (cGAMP) to generate a candidate vaccine, and this vaccine elicits stronger systemic and mucosal humoral immunity than vaccines containing other forms of the S protein. Furthermore, the candidate vaccine administered via intranasal route can enhance local immune responses in the respiratory tract. Importantl

Measles Virus Genotype D Wild Strains Suppress Interferon-Stimulated Gene Expression More Potently than Laboratory Strains in SiHa Cells.

Changes in interferon (IFN)-stimulated gene (ISG) expression in cells infected with measles virus (MeV), four wild strains (belonging to different genotypes), and the laboratory strain Edmonston were examined. ISGs [MxA, 2'-5'-oligoadenylate synthetase, and interferon regulatory factor-1] were upregulated in an MeV-infection-induced manner and in an IFN-induced manner. In MeV-infected SiHa cell lines, the MeV infection-induced expression levels were in the order of A>H1>D8>D5>D3. On the other hand, all infected cell lines abolished type I and III IFN-induced ISG expression. However, partial ty

MHC class II-associated invariant chain linkage of antigen dramatically improves cell-mediated immunity induced by adenovirus vaccines.

The ideal vaccine induces a potent protective immune response, which should be rapidly induced, long-standing, and of broad specificity. Recombinant adenoviral vectors induce potent Ab and CD8+ T cell responses against transgenic Ags within weeks of administration, and they are among the most potent and versatile Ag delivery vehicles available. However, the impact of chronic infections like HIV and hepatitis C virus underscore the need for further improvements. In this study, we show that the protective immune response to an adenovirus-encoded vaccine Ag can be accelerated, enhanced, broadened

Induction of SARS-CoV-2 neutralizing antibodies by CoronaVac and BNT162b2 vaccines in naïve and previously infected individuals.

BACKGROUND: A major challenge of the SARS-CoV-2 pandemic is to better define "protective thresholds" to guide the global response. We aimed … or both vaccines. METHODS: We determined and compared the longitudinal neutralizing (nAb) and anti-nucleocapsid (anti-N) antibody responses of 74 COVID-19 individuals (37 outpatient and 37 hospitalized) during the acute disease and convalescence. We also assessed the antibody boosting of 36 of these individuals who were immunized after convalescence with eith …

[An Important Problem in AdV-36 Seropositive Obesity Patients: Leptin Resistance].

Adenoviruses are naked viruses with an icosahedral nucleocapsid containing a 36 kb linear double-stranded DNA genome that encodes 30-40 proteins. The word "obesity" in Latin means "because of feeding". Obesity is an energy metabolism pathology that paves the way for physical and psychological problems with excessive fat accumulation that can impair health. Body mass index (BMI), unaffected by gender and age, is the most useful indicator of overweight and obesity at the population level. The concept of infectobesity was first introduced in 1978 after the data showed that viruses might also play…

Vaccination with DNA encoding internal proteins of influenza virus does not require CD8(+) cytotoxic T lymphocytes: either CD4(+) or CD8(+) T cells can promote survival and recovery after challenge.

DNA vaccination offers the advantages of viral gene expression within host cells without the risks of infectious virus. Like viral vaccines, DNA vaccines encoding internal influenza virus proteins can induce immunity to conserved epitopes and so may defend the host against a broad range of viral variants. CD8(+) cytotoxic T lymphocytes (CTL) have been described as essential effectors in protection by influenza nucleoprotein (NP), although a lesser role of CD4(+) cells has been reported. We immunized mice with plasmids encoding influenza virus NP and matrix (M). NP + M DNA allowed B6 mice to su

Mammalian adaptation of influenza A(H7N9) virus is limited by a narrow genetic bottleneck.

Human infection with avian influenza A(H7N9) virus is associated mainly with the exposure to infected poultry. The factors that allow interspecies transmission but limit human-to-human transmission are unknown. Here we show that A/Anhui/1/2013(H7N9) influenza virus infection of chickens (natural hosts) is asymptomatic and that it generates a high genetic diversity. In contrast, diversity is tightly restricted in infected ferrets, limiting further adaptation to a fully transmissible form. Airborne transmission in ferrets is accompanied by the mutations in PB1, NP and NA genes that reduce viral

Immunization with influenza A NP-expressing vaccinia virus recombinant protects mice against experimental infection with human and avian influenza viruses.

Two-fold immunization of Balb/c mice with a vaccinia virus recombinant expressing the NP protein of influenza A/PR8/34 (H1N1) virus under the control of a strong synthetic promoter induced specific antibodies and protected animals against low-dose challenge by mouse-adapted heterosubtypic variants of human A/Aichi2/68 (H3N2) and avian A/Mallard/Pennsylvania/10218/84 (H5N2) influenza virus strains. The surviving immunized animals had lower anti-hemagglutinin antibody titers compared to non-immunized mice. There was no difference in viral titers in lungs of immunized and non-immunized animals th

Withholding methotrexate after vaccination with ChAdOx1 nCov19 in patients with rheumatoid or psoriatic arthritis in India (MIVAC I and II): results of two, parallel, assessor-masked, randomised controlled trials.

BACKGROUND: There is a necessity for an optimal COVID-19 vaccination strategy for vulnerable population groups, including people with autoim … te for the preceding 6 weeks. Those with previous COVID-19 or who were positive for anti-SARS-CoV-2 nucleocapsid antibodies were excluded from the trials. People on high-dose corticosteroids and rituximab were also excluded, whereas other disease-modifying antirheumatic drugs were allowed. In MIVAC I, participants were randomly assigned (1:1) to stop methotrex …

Sotrovimab versus usual care in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial.

BACKGROUND: Sotrovimab is a neutralising monoclonal antibody targeting the SARS-CoV-2 spike protein. We aimed to evaluate the efficacy and s … ipants were retrospectively categorised as having a high antigen level if baseline serum SARS-CoV-2 nucleocapsid antigen was above the median concentration (the prespecified primary efficacy population), otherwise they were categorised as having a low antigen level. The primary outcome was 28-day mortality assessed by intention to treat. Safety outcomes were a …

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study.

INTRODUCTION: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aime … -19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MR …

Activation of cross-reactive mucosal T and B cell responses in human nasopharynx-associated lymphoid tissue in vitro by Modified Vaccinia Ankara-vectored influenza vaccines.

UNLABELLED: Recent efforts have been focused on the development of vaccines that could induce broad immunity against influenza virus, either through T cell responses to conserved internal antigens or B cell response to cross-reactive haemagglutinin (HA). We studied the capacity of Modified Vaccinia Ankara (MVA)-vectored influenza vaccines to induce cross-reactive immunity to influenza virus in human nasopharynx-associated lymphoid tissue (NALT) in vitro. Adenotonsillar cells were isolated and stimulated with MVA vaccines expressing either conserved nucleoprotein (NP) and matrix protein 1 (M1)

Characteristic amino acid changes of influenza A(H1N1)pdm09 virus PA protein enhance A(H7N9) viral polymerase activity.

Human coinfection with a novel H7N9 influenza virus and the 2009 pandemic A(H1N1) influenza virus, H1N1pdm09, has recently been reported in China. Because reassortment can occur during coinfection, it is necessary to clarify the effects of gene reassortment between these two viruses. Among the viral ribonucleoprotein complex (vRNP) genes, only the PA gene of H1N1pdm09 enhances the avian influenza viral polymerase activity. Based on a phylogenetic analysis, we show a special evolutionary feature of the H1N1pdm09 PA gene, which clustered with those of the novel H7N9 virus and related H9N2 viruse

Lung histopathological findings in fatal pandemic influenza A (H1N1).

OBJECTIVE: To describe the lung pathological changes in influenza A (H1N1) viral pneumonia. We studied morphological changes, nitro-oxidative stress and the presence of viral proteins in lung tissue. METHODS AND PATIENTS: Light microscopy was used to examine lung tissue from 6 fatal cases of pandemic influenza A (H1N1) viral pneumonia. Fluorescence for oxidized dihydroethydium, nitrotyrosine, inducible NO synthase (NOS2) and human influenza A nucleoprotein (NP) (for analysis under confocal microscopy) was also studied in lung tissue specimens. RESULTS: Age ranged from 15 to 50 years. Three p

An optimized assay for the enumeration of antigen-specific memory B cells in different compartments of the human body.

OBJECT: In the framework of our current study we set out to develop an optimized assay for the quantification of antigen-specific B cells in different compartments of the human body. METHODS: Mononuclear cells (MNC) derived from the peripheral blood, bone marrow (BM), or human tonsils were incubated with different combinations of stimuli. The stimulated cells and culture supernatants were then applied to IgG-ELISPOT and ELISA read-out assays and tetanus toxoid (TT)-specific B cell responses were quantified. RESULTS: We found that a combination of CD40L, CpG, and IL21 was optimal for the indu

Outcome of transforaminal epidural steroid injection for lumbar radiculopathy: initial three-year experience at Upendra Devkota Memorial-National Institute of Neurological and Allied Sciences, Nepal.

INTRODUCTION: Additional risk minimisation measures (aRMMs) for medicinal products are necessary to address specific important safety issues which may not be practically achieved through routine risk management measures alone. The implementation and determination of effectiveness for aRMMs can be a challenge as it involves multiple stakeholders. It is therefore important to have concise objectives to avoid undue burden on patients, healthcare professionals and the healthcare system. AIM: The aim of this study was to examine how aRMMs are implemented and how effectiveness is assessed in the Eu

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… It was reported that this electrochemical biosensor was able to detect viral antigen nucleocapsid protein, IgM and IgG antibodies, and the inflammatory biomarker C-reactive protein (CRP). … The specific IgG of SARS-CoV-2 was captured by dispensing the virus’s nucleocapsid phosphoprotein onto a nitrocellulose membrane. This biosensor was also used for some clinical samples tested by RT-PCR before. …

HIV-1 replication.

In general terms, the replication cycle of lentiviruses, including HIV-1, closely resembles that of other retroviruses. There are, however, … iral protease (PR) to the mature Gag proteins matrix (also known as MA or p17), capsid (CA or p24), nucleocapsid (NC or p7), and p6. Two spacer peptides, p2 and p1, are also generated upon Pr55Gag processing. The pol-encoded enzymes are initially synthesized as part of a large polyprotein precursor, Pr160GagPol, whose synthesis results from a rare frameshiftin …

Emerging strategies and therapies for treatment of Paget's disease of bone.

Paget's disease of bone (PDB) is a progressive monostotic or polyostotic metabolic bone disease characterized by focal abnormal bone remodeling, with increased bone resorption and excessive, disorganized, new bone formation. PDB rarely occurs before middle age, and it is the second most frequent metabolic bone disorder after osteoporosis, affecting up to 3% of adults over 55 years of age. One of the most striking and intriguing clinical features is the focal nature of the disorder, in that once the disease is established within a bone, there is only local spread within that bone and no systemi

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… Measles virus nucleocapsid protein Osteoclasts in PDB are increased in number and size and express a “pagetic phenotype” that distinguishes them from normal osteoclasts. … Osteoclasts expressing the measles virus nucleocapsid gene display a pagetic phenotype. J Clin Invest. 2000;105(5):607–614. doi: 10.1172/JCI8489. 101. Kurihara N, Hiruma Y, Yamana K, et al. Contributions of the measles virus nucleocapsid gene and the SQSTM1/p62(P392L) mutation to Paget’s disease. …