Adult indication 13-valent pneumococcal conjugate vaccine clinical development overview: formulation, safety, immunogenicity (dosing and sequence), coadministration, and efficacy.

Introduction: There was no 13-valent pneumococcal conjugate vaccine (PCV13) adult antibody concentration threshold regulatory criterion for licensure - unlike the pediatric indication; consequently, for the adult indication, PCV13 serotype-specific opsonophagocytic activity (OPA) geometric mean titer (GMT) values were immunobridged to the 23-valent plain polysaccharide vaccine (PPV23) to infer efficacy against invasive pneumococcal disease (IPD). Subsequently, a double-blind, randomized, controlled PCV13 efficacy trial (CAPiTA) was performed in community-living, older adults to confirm efficacy against vaccine-serotype IPD (VT-IPD) and establish efficacy against vaccine-serotype pneumococcal community-acquired pneumonia (VT-CAP).

Areas Covered: This article summarizes 31 publications from the PCV13 adult indication clinical development trials and other PCV13 clinical studies, organized by formulation, reactogenicity and safety, immunogenicity, coadministration, and clinical efficacy.

The Apparent Activation Energy of a Novel Low-Calcium Silicate Hydraulic Binder.

In this work, the apparent activation energy () of a novel low-calcium binder was, for the first time, experimentally determined, using a calorimetric approach. Additionally, a correlation between the , measured at the acceleration period with the C/S ratio of the hydration product is proposed. The of the prepared pastes was determined through isothermal calorimetry tests by calculating the specific rate of reaction at different temperatures, using two different approaches.

Electrical stimulation of neural-differentiating iPSCs on novel coaxial electroconductive nanofibers.

Neural tissue engineering strategies are paramount to create fully mature neurons, necessary for new therapeutic strategies for neurological diseases or the creation of reliable in vitro models. Scaffolds can provide physical support for these neurons and enable cues for enhancing neural cell differentiation, such as electrical current. Coaxial electrospinning fibers, designed to fulfill neural cell needs, bring together an electroconductive shell layer (PCL-PANI), able to mediate electrical stimulation of cells cultivated on fibers mesh surface, and a soft core layer (PGS), used to finetune fiber diameter (951 ± 465 nm) and mechanical properties (1.

Polyaniline-polycaprolactone fibers for neural applications: Electroconductivity enhanced by pseudo-doping.

Replenishing neurons in patients with neurodegenerative diseases is one of the ultimate therapies for these progressive, debilitating and fatal diseases. Electrical stimulation can improve neuron stem cell differentiation but requires a reliable nanopatterned electroconductive substrate. Potential candidate substrates are polycaprolactone (PCL) - polyaniline:camphorsulfonic acid (PANI:CSA) nanofibers, but their nanobiophysical properties need to be finetuned.

Effects of Starch Incorporation on the Physicochemical Properties and Release Kinetics of Alginate-Based 3D Hydrogel Patches for Topical Delivery.

The development of printable hydrogel inks for extrusion-based 3D printing is opening new possibilities to the production of new and/or improved pharmaceutical forms, specifically for topical application. Alginate and starch are natural polysaccharides that have been extensively exploited due to their biocompatibility, biodegradability, viscosity properties, low toxicity, and relatively low cost. This research work aimed to study the physicochemical and release kinetic effects of starch incorporation in alginate-based 3D hydrogel patches for topical delivery using a quality by design approach.

Surface and mechanical properties of a nanostructured citrate hydroxyapatite coating on pure titanium.

The presence of a biomimetic HAP coating on titanium surface, which reduces the structural stiffness, is essential to improve implants biocompatibility and osteointegration. In this study, new citrate-HAP (cHAP) coatings were produced by a simple hydrothermal method on pure titanium (Ti) surface, without requiring any additional pretreatment on this metal surface. The formed cHAP coatings consisting of nanorod-like hydroxyapatite particles, conferred nanoroughness and wettability able to endow improved biological responses.

Relevance of HTLV-1 proviral load in asymptomatic and symptomatic patients living in endemic and non-endemic areas of Argentina.

HTLV-1 proviral load (pVL) in peripheral blood mononuclear cell (PBMCs) is proposed as a marker of disease progression but its role still remains controversial. The aim of this study was to evaluate the levels of HTLV-1 pVL in symptomatic patients and asymptomatic HTLV-1 carriers. In this cross-sectional study the pVL was measured by Real Time PCR in 102 asymptomatic carriers and 22 symptomatic patients (5ATLL, 15 TSP and 2 uveitis).

Influence of Pseudowollastonite on the Performance of Low Calcium Amorphous Hydraulic Binders.

A systematic investigation of the influence of pseudowollastonite on the performance of a new family of low calcium hydraulic binders is described. Samples of the new low calcium binder were produced by an innovative process consisting of heating and homogenizing the mix of raw materials (limestone, sand, and fuel cracking catalyst) at a constant temperature followed by the rapid cooling of the mixture itself. Different maximum temperatures, close to the melting temperature of the mix, were tested, and materials with CaO/SiO (C/S) ratios of 0.

Sterilization of silicone-based hydrogels for biomedical application using ozone gas: Comparison with conventional techniques.

Sterilization of hydrogels is challenging due to their often reported sensitivity to conventional methods involving heat or radiation. Although aseptic manufacturing is a possibility, terminal sterilization is safer in biological terms, leading to a higher overall efficiency, and thus should be used whenever it is possible. The main goal of this work was to study the applicability of an innovative ozone gas terminal sterilization method for silicone-based hydrogels and compare its efficacy and effects with those of traditional sterilization methods: steam heat and gamma irradiation.

Diffusion-Based Design of Multi-Layered Ophthalmic Lenses for Controlled Drug Release.

The study of ocular drug delivery systems has been one of the most covered topics in drug delivery research. One potential drug carrier solution is the use of materials that are already commercially available in ophthalmic lenses for the correction of refractive errors. In this study, we present a diffusion-based mathematical model in which the parameters can be adjusted based on experimental results obtained under controlled conditions.

Drug release from liposome coated hydrogels for soft contact lenses: the blinking and temperature effect.

In this article, liposome-based coatings aiming to control drug release from therapeutic soft contact lenses (SCLs) materials are analyzed. A PHEMA based hydrogel material loaded with levofloxacin is used as model system for this research. The coatings are formed by polyelectrolyte layers containing liposomes of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and DMPC + cholesterol (DMPC + CHOL).

Pneumococcal conjugate vaccine in adults: Let's see what happens.

The recent recommendation for the use of the 13-valent pneumococcal conjugate vaccine (PCV13) in adults 65 y of age and older, provides a new tool for preventing disease in this at-risk population. The conjugate vaccine induces a T-cell dependent response, which distinguishes it from the polysaccharide vaccine and could provide the longer-term protection necessary to have a significant impact in this population.

Controlled Release of Antibiotics From Vitamin E-Loaded Silicone-Hydrogel Contact Lenses.

Symptoms of bacterial and fungal keratitis are typically treated through the frequent application of antibiotic and antifungal eye drops. The high frequency of half hourly or hourly eye drop administration required to treat these indications is tedious and could reduce compliance. Here, we combine in vitro experiments with a mathematical model to develop therapeutic soft contact lenses to cure keratitis by extended release of suitable drugs.

Pneumococcal conjugate vaccine use in adults.

Streptococcus pneumoniae is a leading cause of illness and death in adults. A polysaccharide vaccine has been available for over 30 years, but despite significant use, the public health impact of this vaccine has been limited. The 13-valent pneumococcal conjugate vaccine (PCV13) has been licensed by the US Food and Drug Administration and other international regulatory authorities with the assumption that induction of a T cell-dependent immune response and noninferior immunogenicity to vaccine antigens when compared with the polysaccharide vaccine would be important to satisfy a significant unmet medical need.

About the effect of eye blinking on drug release from pHEMA-based hydrogels: an in vitro study.

The development of new ophthalmic drug delivery systems capable of increasing the residence time of drugs in the eye and improve its bioavailability relatively to eyedrops has been object of intense research in recent years. Several studies have shown that drug-loaded therapeutic soft contact lenses (SCLs) constitute a promising approach, with several potential advantages as compared with collyria. The main objective of this work is to study the effect of repetitive load and friction cycles caused by the eye blinking, on the drug release from hydrogels used in SCLs which, as far as we know, was never investigated before.

Short communication: Emergence of novel A/G recombinant HIV-1 strains in Argentina.

The predominant circulating HIV-1 strains in South America are subtype B and B/F recombinants with different distributions among countries. However, the emergence of other subtypes is a matter of concern and needs continuous monitoring. We identified three different A/G recombinants in Argentina, two of them in vertically infected children from unlinked mothers and one in an adult female.

Effect of plasma treatment on the performance of two drug-loaded hydrogel formulations for therapeutic contact lenses.

Although the plasma technology has long been applied to treat contact lenses, the effect of this treatment on the performance of drug-loaded contact lenses is still unclear. The objective of this work is to study the effect of nitrogen plasma treatment on two drug-loaded polymeric formulations which previously demonstrated to be suitable for therapeutic contact lenses: a poly-hydroxyethylmethacrylate (pHEMA) based hydrogel loaded with levofloxacin and a silicone-based hydrogel loaded with chlorhexidine. Modifications of the surface and the optical properties, and alterations in the drug release profiles and possible losses of the antimicrobial activities of the drugs induced by the plasma treatment were assessed.

Effect of tetracaine on DMPC and DMPC+cholesterol biomembrane models: liposomes and monolayers.

Different types of lipid bilayers/monolayers have been used to simulate the cellular membranes in the investigation of the interactions between drugs and cells. However, to our knowledge, very few studies focused on the influence of the chosen membrane model upon the obtained results. The main objective of this work is to understand how do the nature and immobilization state of the biomembrane models influence the action of the local anaesthetic tetracaine (TTC) upon the lipid membranes.

Comparison of two hydrogel formulations for drug release in ophthalmic lenses.

In the present work two types of polymers were investigated as drug releasing contact lens materials: a poly-hydroxyethylmethacrylate (pHEMA) based hydrogel and a silicone hydrogel. The silicone hydrogel resulted from the addition of TRIS, a hydrophobic monomer containing silicon (3-tris(trimethylsilyloxy)silylpropyl 2-methylprop-2-enoate), to pHEMA. Both hydrogels were loaded with an antibiotic (levofloxacin) and an antiseptic (chlorhexidine) by soaking in the drug solutions.

Distribution of 13-valent pneumococcal conjugate vaccine Streptococcus pneumoniae serotypes in US adults aged ≥50 years with community-acquired pneumonia.

Background: Streptococcus pneumoniae causes a substantial proportion of community-acquired pneumonia (CAP) and healthcare-associated pneumonia (HCAP) in the United States. Limited data are available regarding the pneumococcal serotypes causing CAP and HCAP.

Methods: Adults aged ≥ 50 years presenting to participating US hospitals with radiographically confirmed pneumonia between February 2010 and September 2011 were screened for inclusion.

Immune response to 13-valent pneumococcal conjugate vaccine with a reduced dosing schedule.

Background: The 7-valent pneumococcal conjugate vaccine (PCV7) has demonstrated effectiveness against pneumococcal illnesses when administered as 3 infant doses plus a toddler dose (3+1 schedule) or as an abbreviated schedule of 2 infant doses plus a toddler dose (2+1 schedule). The 13-valent pneumococcal conjugate vaccine (PCV13) is approved and World Health Organization-prequalified for administration in a 2+1 schedule when used as part of routine immunization programs.

Objective: To summarize immunologic responses elicited by PCV13 administered in a 2+1 schedule and following 2 doses in a 3+1 schedule.

Pneumococcal conjugate vaccine for adults: a new paradigm.

A 13-valent pneumococcal conjugate vaccine has been studied in adults aged ≥ 50 years to compare the immune response to that induced by the 23-valent pneumococcal polysaccharide vaccine, which has been the standard of care over the past 30 years. The results demonstrate that adults, regardless of whether they are naive or previously vaccinated with the polysaccharide vaccine, have an overall superior antibody response when vaccinated with the conjugate vaccine compared with the pneumococcal polysaccharide vaccine. More importantly, the nature of the response is indicative of a T-cell-dependent response that elicits immunological memory and, therefore, primes the immune system for either natural exposure or subsequent booster vaccination with either conjugate or polysaccharide vaccine.

Interaction of local and general anaesthetics with liposomal membrane models: a QCM-D and DSC study.

The behaviour of four local anaesthetics (lidocaine, levobupivacaine, ropivacaine and tetracaine) and one general anaesthetic (propofol) is compared when interacting with two types of model membranes: supported layers of liposomes and liposomes in solution. Several liposomal compositions were tested: dimyristoylphosphatidylcholine (DMPC), binary mixtures of DMPC with cholesterol (CHOL), and ternary mixtures of dipalmitoylphosphatidylcholine (DPPC), DMPC, and CHOL. A quartz crystal microbalance with dissipation, QCM-D, was used to assess changes in the properties of supported layers of liposomes.