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C Patrick McAtee, Christopher A Seid, Molly Hammond, Elissa Hudspeth, Brian P Keegan, Zhuyun Liu, Junfei Wei, Bin Zhan, Raul Arjona-Sabido, Vladimir Cruz-Chan, Eric Dumonteil, Peter J Hotez, Maria Elena Bottazzi
The nucleoside hydrolase gene from Leishmania donovani was cloned and expressed in Escherichia coli as a full length 36-kDa protein (LdNH36). Following lysis and extraction, the protein was purified by anion exchange and gel filtration chromatography. The purified protein had a molecular mass of approximately 36-kDa and was confirmed to be >99% pure. Using a nucleoside hydrolase assay, the protein was found to exhibit a Km of 741 ± 246 μM. Protein integrity was confirmed by lithium dodecyl sulfate polyacrylamide gel electrophoresis (LDS-PAGE), mass spectrometry (MS), and enzymatic assay...
October 20, 2016: Protein Expression and Purification
Anthony L Cunningham, Nathalie Garçon, Oberdan Leo, Leonard R Friedland, Richard Strugnell, Béatrice Laupèze, Mark Doherty, Peter Stern
In the 21st century, an array of microbiological and molecular allow antigens for new vaccines to be specifically identified, designed, produced and delivered with the aim of optimising the induction of a protective immune response against a well-defined immunogen. New knowledge about the functioning of the immune system and host pathogen interactions has stimulated the rational design of vaccines. The design toolbox includes vaccines made from whole pathogens, protein subunits, polysaccharides, pathogen-like particles, use of viral/bacterial vectors, plus adjuvants and conjugation technology to increase and broaden the immune response...
October 18, 2016: Vaccine
Karen K Yam, Angela Brewer, Virginie Bleau, Édith Beaulieu, Corey P Mallett, Brian J Ward
We investigated the long-term immune profiles of dose-sparing, AS03-adjuvanted vaccines compared to a traditional high-dose, unadjuvated influenza vaccine formulations. BALB/c mice received 2 IM injections of influenza A/Uruguay/716/2007 (H3N2) split vaccine antigen: high-dose (HD) (3 µg hemagglutinin (HA)/dose) or low-dose (LD) formulations (0.03 µg or 0.003 µg HA) with AS03 and were followed to 34 weeks post-boost (pb). We examined serologic responses, spleen and bone marrow (BM) HA-specific antibody-secreting cells (ASCs) by ELISpot, influenza-specific cytokine/chemokine production in re-stimulated splenocytes by multiplex ELISA, and antigen-specific CD4+ T cells that express cytokines (IL-2, IFNγ, TNFa and IL-5) by flow cytometry...
October 21, 2016: Human Vaccines & Immunotherapeutics
Magda Yehia El Seify, Eman Mahmoud Fouda, Hanan Mohamed Ibrahim, Maha Muhammad Fathy, Asmaa Al Husseiny Ahmed, Walaa Shawky Khater, Noha Nagi Mohammed Salah El Deen, Heba Galal Mohamed Abouzeid, Nancy Riyad Ahmed Hegazy, Heba Salah Sayed Elbanna
BACKGROUND: While recognizing the etiology of community-acquired pneumonia is necessary for formulating local antimicrobial guidelines, limited data is published about this etiology in Egyptian pediatric patients. OBJECTIVES: To determine the frequency of bacterial and viral pathogens causing community-acquired pneumonia (CAP) among immunocompetent Egyptian infants and preschool children. METHODS: Ninety infants and preschool-age children admitted to our hospital with CAP were prospectively included in the study...
September 29, 2016: European Journal of Microbiology & Immunology
Kaori Sadakane, Takamichi Ichinose, Masataka Nishikawa, Hirohisa Takano, Takayuki Shibamoto
BACKGROUND: Epidemiological studies have implicated Asian sand dust (ASD) in the increased prevalence of respiratory disorders, including asthma. It has been observed that fungal elements such as β-glucan can be adsorbed onto ASD. In the present study, the exacerbating effect of the combined exposure to zymosan A (ZymA) containing yeast β-glucan and heat-inactivated ASD on ovalbumin (OVA)-induced murine lung eosinophilia was investigated. METHODS: BALB/c mice were repeatedly instilled intratracheally with one of eight immunogenic formulations consisting of various combinations of (1) ZymA, (2) ASD that was briefly heated to remove organic substances (H-ASD), and (3) OVA in normal saline, or each of the above alone...
2016: Allergy, Asthma, and Clinical Immunology
Stefan W Metz, Shaomin Tian, Gabriel Hoekstra, Xianwen Yi, Michelle Stone, Katie Horvath, Michael J Miley, Joseph DeSimone, Chris J Luft, Aravinda M de Silva
Dengue virus (DENV) is the causative agent of dengue fever and dengue hemorrhagic fever. The virus is endemic in over 120 countries, causing over 350 million infections per year. Dengue vaccine development is challenging because of the need to induce simultaneous protection against four antigenically distinct DENV serotypes and evidence that, under some conditions, vaccination can enhance disease due to specific immunity to the virus. While several live-attenuated tetravalent dengue virus vaccines display partial efficacy, it has been challenging to induce balanced protective immunity to all 4 serotypes...
October 2016: PLoS Neglected Tropical Diseases
Roberto Hegg, André Mattar, João Nunes de Matos-Neto, José Luiz Pedrini, Sabina Bandeira Aleixo, Roberto Odebrecht Rocha, Renato Peixoto Cramer-Junior, Sylvie van-Eyll-Rocha
OBJECTIVES: To compare the efficacy and safety of two filgrastim formulations for controlling chemotherapy-induced neutropenia and to evaluate the non-inferiority of the test drug relative to the originator. METHODS: This phase III non-inferiority study had a randomized, multicenter, and open-label design. The patients were randomized at a ratio of 1:1 with a follow-up period of 6 weeks for each patient. In both study arms, filgrastim was administered subcutaneously at a daily dose of 5 mg/kg body weight...
October 1, 2016: Clinics
Wing-Hin Lee, Ching-Yee Loo, Chean-Ring Leong, Paul M Young, Daniela Traini, Ramin Rohanizadeh
The effectiveness of conventional cancer chemotherapy is hampered by the occurrence of multidrug resistance (MDR) in tumor cells. Although many studies have reported the development of novel MDR chemotherapeutic agents, clinical success is lacking owing to the high associated toxicity. Nanoparticle-based delivery of chemotherapeutic drugs has emerged as alternative approach to treat MDR cancers via exploitation of leaky vasculature in the tumor microenvironment. Accordingly, functionalization of nanoparticles with target specific ligands can be employed to achieve significant improvements in the treatment of MDR cancer...
October 19, 2016: Expert Opinion on Drug Delivery
Patricia Rubio Reyes, Natalie A Parlane, D Neil Wedlock, Bernd H A Rehm
Traditional approaches to vaccine development have failed to identify better vaccines to replace or supplement BCG for the control of tuberculosis (TB). Subunit vaccines offer a safer and more reproducible alternative for the prevention of diseases. In this study, the immunogenicity of bacterially derived polyester beads displaying three different Rv antigens of Mycobacterium tuberculosis was evaluated. Polyester beads displaying the antigens Rv1626, Rv2032, Rv1789, respectively, were produced in an endotoxin-free Escherichia coli strain...
October 13, 2016: International Journal of Medical Microbiology: IJMM
Domenico Otranto, Greg Johnson, Kevin Syvrud, Stephen Yoon, James S Hunter, Steffen Rehbein
BACKGROUND: The studies reported here were conducted to assess the efficacy of ivermectin long-acting injection (IVM LAI; IVOMEC® GOLD, Merial; 3.15 % w/v ivermectin) for the treatment and control of natural infestations of cattle by Hypoderma bovis and Hypoderma lineatum, which are the most economically important oestrid flies of cattle in the northern hemisphere. METHODS: Cattle selected from herds with a history of Hypoderma infestation were grouped into blocks of three (Italy, 33 cattle; Germany, 30 cattle) or two (USA, 16 cattle) animals each, on the basis of positivity at the pre-treatment anti-Hypoderma antibody titres...
October 18, 2016: Parasites & Vectors
Jessica Martin, Mark Wilcox
PURPOSE OF REVIEW: Clostridium difficile infection has attained high prominence given its prevalence and impacts on patients and healthcare institutions. Multiple new approaches to the prevention and treatment of C. difficile infection (CDI) are undergoing clinical trials. RECENT FINDINGS: Bezlotoxumab is a monoclonal antibody against toxin B that has successfully completed phase III studies, demonstrating a significant reduction in recurrent CDI when given with standard of care antibiotics...
October 7, 2016: Current Opinion in Infectious Diseases
Kawsar R Talaat, Ruth D Ellis, Janet Hurd, Autumn Hentrich, Erin Gabriel, Noreen A Hynes, Kelly M Rausch, Daming Zhu, Olga Muratova, Raul Herrera, Charles Anderson, David Jones, Joan Aebig, Sarah Brockley, Nicholas J MacDonald, Xiaowei Wang, Michael P Fay, Sara A Healy, Anna P Durbin, David L Narum, Yimin Wu, Patrick E Duffy
Transmission-blocking vaccines (TBVs) that target sexual stage parasite development could be an integral part of measures for malaria elimination. Pfs25 is a leading TBV candidate, and previous studies conducted in animals demonstrated an improvement of its functional immunogenicity after conjugation to EPA, a recombinant, detoxified ExoProtein A from Pseudomonas aeruginosa. In this report, we describe results of an open-label, dose-escalating Phase 1 trial to assess the safety and immunogenicity of Pfs25-EPA conjugates formulated with Alhydrogel®...
2016: PloS One
Peter Nash, Johan Vanhoof, Stephen Hall, Udayasankar Arulmani, Rita Tarzynski-Potempa, Kristina Unnebrink, Andrew N Payne, Alfred Cividino
INTRODUCTION: Adalimumab, an anti-tumor necrosis factor antibody, is currently available in a 40 mg/0.8 mL formulation. The objective of this analysis was to evaluate injection site-related pain, safety, and tolerability of a 40 mg/0.4 mL formulation of adalimumab that had fewer excipients, a smaller volume, and a delivery presentation with a smaller gauge needle, versus the current 40 mg/0.8 mL formulation in patients with rheumatoid arthritis (RA). METHODS: Two identically designed, phase 2, randomized, single-blind, two-period crossover studies were conducted in Belgium and the Czech Republic (Study 1) and Australia, Canada, and Germany (Study 2)...
August 18, 2016: Rheumatol Ther
C Metochis, I Spanos, N Auchinachie, V O Crampton, J G Bell, A Adams, K D Thompson
Juvenile salmon, with an initial weight of 9 g, were fed three experimental diets, formulated to replace 35 (SPC35), 58 (SPC58) and 80 (SPC80) of high quality fishmeal (FM) with soy protein concentrate (SPC) in quadruplicate tanks. Higher dietary SPC inclusion was combined with increased supplementation of methionine, lysine, threonine and phosphorus. The experiment was carried out for 177 days. On day 92 salmon in each tank were bulk weighed. Post weighing eighty salmon from each tank were redistributed in two sets of 12 tanks...
October 11, 2016: Fish & Shellfish Immunology
August Cesarec, Robert Likić
BACKGROUND AND OBJECTIVE: Breast cancer is the most common cancer in women and has considerable impact on healthcare budgets and patients' quality of life. Trastuzumab (Herceptin(®)) is a monoclonal antibody directed against the human epidermal growth factor receptor (HER2) for the treatment of breast cancer. Several trastuzumab biosimilars are currently in development. In 2015, trastuzumab was the drug with the highest financial consumption among all drugs in Croatia. This model estimates the 1-year budget impact of the introduction of biosimilar trastuzumab in Croatia...
October 11, 2016: Applied Health Economics and Health Policy
Anjaneya Ayanur, Karam Pal Singh, Susan Cherian, Vidya Singh, Sukdeb Nandi, Mani Saminathan, Khorajiya Jaynudin, Jeet SinghYadav, Rajendra Singh, Ashok Kumar Tiwari
Bluetongue (BT) is a non‑contagious arthropod‑borne viral disease of domestic and wild ruminants. It is endemic to India and clinical outbreaks of disease have been reported mainly in sheep, although BT is often asymptomatic in other ruminant species. In the present serological survey, a total of 576 serum samples, comprising of 416 cattle and 160 sheep, covering different agro‑climatic zones of Rajasthan, Uttar Pradesh, and Karnataka states, were screened for the presence of Bluetongue virus (BTV) specific antibodies using competitive enzyme‑linked immunosorbent assay (c‑ELISA)...
September 30, 2016: Veterinaria Italiana
Kevin K Ariën, Françoise Baleux, Delphine Desjardins, Françoise Porrot, Yves-Marie Coïc, Johan Michiels, Kawthar Bouchemal, David Bonnaffé, Timothée Bruel, Olivier Schwartz, Roger Le Grand, Guido Vanham, Nathalie Dereuddre-Bosquet, Hugues Lortat-Jacob
The CD4 and the cryptic coreceptor binding sites of the HIV-1 envelope glycoprotein are key to viral attachment and entry. We developed new molecules comprising a CD4 mimetic peptide linked to anionic compounds (mCD4.1-HS12 and mCD4.1-PS1), that block the CD4-gp120 interaction and simultaneously induce the exposure of the cryptic coreceptor binding site, rendering it accessible to HS12- or PS1- mediated inhibition. Using a cynomolgus macaque model of vaginal challenge with SHIV162P3, we report that mCD4.1-PS1, formulated into a hydroxyethyl-cellulose gel provides 83% protection (5/6 animals)...
October 10, 2016: Scientific Reports
Steven R Wiley, Vanitha S Raman
Adjuvants in vaccine formulations are designed to enhance immune responses against a target antigen or pathogen. The ability of these vaccines to induce activation and differentiation of mature naïve B cells to produce pathogen-specific antibodies (immunoglobulins; Ig) helps guarantee long-lived humoral immunity. This process involves clonal expansion of antigen-specific B cells, genomic rearrangement of Ig heavy (IgH) and light (IgL) loci, somatic hypermutation (SHM), and clonal selection for affinity-matured antibody, resulting in a vast but directed repertoire of B cells expressing highly specific antibody proteins...
2017: Methods in Molecular Biology
Livia Brunner, Christophe Barnier-Quer, Nicolas Collin
QS-21, a saponin extracted from the tree Quillaja saponaria Molina, is a vaccine adjuvant which has been shown to elicit robust antibody and cell-mediated immune responses in a variety of preclinical and clinical studies [1]. Its purification from the natural source is a lengthy and difficult process. The commercially available saponin mixture Quil-A(®) is a fraction of the bark extract containing a variety of saponins, including QS-21. In order to facilitate access to QS-21 at laboratory-scale amounts, we propose here a method of purification of QS-21 starting from Quil-A(®)...
2017: Methods in Molecular Biology
Zuyi Chen, Yaling Jing, Qiang Wen, Xianping Ding, Shun Zhang, Tao Wang, Yiwen Zhang, Jianhui Zhang
BACKGROUND: Cervical cancer is associated with infection by certain subtypes of human papillomavirus (HPV). The L1 protein comprising HPV vaccine formulations elicits high-titre neutralizing antibodies and confers protection against specific HPV subtypes. HPV L2 protein is an attractive candidate for cross-protective vaccines. HPV-33 and HPV-58 are very prevalent among Chinese women. METHODS: To study the gene intratypic variations and polymorphisms of HPV-33 and HPV-58 L1/L2 in Sichuan China, HPV-33 and HPV-58 L1 and L2 genes were sequenced and compared with other genes submitted to GenBank...
October 7, 2016: Virology Journal
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