Search results for "vaccine."
showing 10 items of 789 documents
The Rotavirus Vaccine Landscape, an Update
2021
Rotavirus is the leading cause of severe acute childhood gastroenteritis, responsible for more than 128,500 deaths per year, mainly in low-income countries. Although the mortality rate has dropped significantly since the introduction of the first vaccines around 2006, an estimated 83,158 deaths are still preventable. The two main vaccines currently deployed, Rotarix and RotaTeq, both live oral vaccines, have been shown to be less effective in developing countries. In addition, they have been associated with a slight risk of intussusception, and the need for cold chain maintenance limits the accessibility of these vaccines to certain areas, leaving 65% of children worldwide unvaccinated and …
Diagnostic and vaccine strategies to prevent infections in patients with inflammatory bowel disease.
2016
Summary Objectives The treatment of inflammatory bowel disease (IBD) has been revolutionized by the use of immunomodulatory agents. Although these potent drugs are effective in controlling disease activity, they also cause an increased risk of new infections or reactivation of latent infections. On these premises, we aimed to provide guidance on the definitions of immunocompromised patients, opportunistic infections and the risk factors associated with their occurrence in an IBD context, and to suggest the proper screening tests for infectious diseases and the vaccination schedules to perform before and/or during therapy with immunomodulators. Methods All the most recent evidences – filtere…
Cost-Effectiveness of Pneumococcal Vaccination of Older People: A Study in 5 Western European Countries
1999
Pneumococcal vaccination of older persons is thought to be cost-effective in preventing pneumococcal pneumonia, but evidence of clinical protection is uncertain. Because there is better evidence of vaccination effectiveness against invasive pneumococcal disease, we determined the cost-effectiveness of pneumococcal vaccination of persons agedor =65 years in preventing hospital admission for both invasive pneumococcal disease and pneumococcal pneumonia in 5 western European countries. In the base case analyses, the cost-effectiveness ratios for preventing invasive disease varied from approximately 11,000 to approximately 33,000 European currency units (ecu) per quality-adjusted life year (QAL…
HBV core particles as a carrier for B cell/T cell epitopes.
2001
In the middle 80s, recombinant hepatitis B virus cores (HBc) gave onset to icosahedral virus-like particles (VLPs) as a basic class of non-infectious carriers of foreign immunological epitopes. The recombinant HBc particles were used to display immunodominant epitopes of hepatitis B, C, and E virus, human rhinovirus, papillomavirus, hantavirus, and influenza virus, human and simian immunodeficiency virus, bovine and feline leukemia virus, foot-and-mouth disease virus, murine cytomegalovirus and poliovirus, and other virus proteins, as well as of some bacterial and protozoan protein epitopes. Practical applicability of the HBc particles as carriers was enabled by their ability to high level …
N‐Terminal Modification of Gly‐His‐Tagged Proteins with Azidogluconolactone
2021
Site-specific protein modifications are vital for biopharmaceutical drug development. Gluconoylation is a non-enzymatic, post-translational modification of N-terminal HisTags. We report high-yield, site-selective inâ vitro α-aminoacylation of peptides, glycoproteins, antibodies, and virus-like particles (VLPs) with azidogluconolactone at pHâ 7.5 in 1â h. Conjugates slowly hydrolyse, but diol-masking with borate esters inhibits reversibility. In an example, we multimerise azidogluconoylated SARS-CoV-2 receptor-binding domain (RBD) onto VLPs via click-chemistry, to give a COVID-19 vaccine. Compared to yeast antigen, HEK-derived RBD was immunologically superior, likely due to observed diffe…
Combining reactive triblock copolymers with functional cross-linkers: A versatile pathway to disulfide stabilized-polyplex libraries and their applic…
2017
Therapeutic nucleic acids such as pDNA hold great promise for the treatment of multiple diseases. These therapeutic interventions are, however, compromised by the lack of efficient and safe non-viral delivery systems, which guarantee stability during blood circulation together with high transfection efficiency. To provide these desired properties within one system, we propose the use of reactive triblock copolypept(o)ides, which include a stealth-like block for efficient shielding, a hydrophobic block based on reactive disulfides for cross-linking and a cationic block for complexation of pDNA. After the complexation step, bifunctional cross-linkers can be employed to bio-reversibly stabiliz…
Trimeric HIV Env provides epitope occlusion mediated by hypervariable loops
2014
AbstractHypervariable loops of HIV-1 Env protein gp120 are speculated to play roles in the conformational transition of Env to the receptor binding-induced metastable state. Structural analysis of full-length Env-based immunogens, containing the entire V2 loop, displayed tighter association between gp120 subunits, resulting in a smaller trimeric diameter than constructs lacking V2. A prominent basal quaternary location of V2 and V3′ that challenges previous reports would facilitate gp41-independent gp120-gp120 interactions and suggests a quaternary mechanism of epitope occlusion facilitated by hypervariable loops. Deletion of V2 resulted in dramatic exposure of basal, membrane-proximal gp41…
The structure of Yersinia pestis Caf1 polymer in free and adjuvant bound states
2010
Caf1 of the plague bacterium, Yersinia pestis is a polymeric virulence factor and vaccine component, formed from monomers by a donor strand exchange (DSE) mechanism. Here, EM images of Caf1 reveal flexible polymers up to 1.5 microm long (4MDa). The bead-like structures along the polymer are 5.8 + or - 1 nm long and correspond to single Caf1 proteins. Short polymers often form circles, presumably by DSE. We also provide the first images of proteins bound to alhydrogel adjuvant. Caf1, hemocyanin and anthrax PA are all resolved clearly and Caf1 exhibits adjuvant bound stretches with long intervening loops draped from the edges.
A molecular assembly system that renders antigens of choice highly repetitive for induction of protective B cell responses.
2002
Virus like particles (VLPs) are known to induce potent B cell responses in the absence of adjuvants. Moreover, epitope-specific antibody responses may be induced by VLPs that contain peptides inserted in their immunodominant regions. However, due to steric problems, the size of the peptides capable of being incorporated into VLPs while still permitting capsid assembly, is rather limited. While peptides genetically fused to either the N- or C-terminus of VLPs present fewer assembly problems, the immune responses obtained against such epitopes are often limited, most likely because the epitopes are not optimally exposed. In addition, such particles may be less stable in vivo. Here, we show th…
Pharmacology and safety of tofacitinib in ulcerative colitis.
2020
The use of Janus kinase (JAK) inhibitors is a new approach in the therapy of inflammatory diseases with immune base. Tofacitinib is one of these inhibitors targeting JAK1 and JAK3, and its efficacy has been demonstrated in the treatment of moderate to severe ulcerative colitis (UC). It is a small synthetic molecule administered orally, with a fast bioavailability and elimination rate, predictable pharmacokinetics and lack of immunogenicity, which are convenient characteristics for both efficacy and safety. This article reviews the pharmacological characteristics of tofacitinib and its safety profile.