Development of adjuvanted recombinant zoster vaccine and its implications for shingles prevention.

Introduction: GSK has developed a two-dose adjuvanted recombinant zoster vaccine (Shingrix, RZV) to protect people aged ≥50 years (50+) against herpes zoster (HZ) and its complications. RZV showed >90% efficacy against HZ, sustained over 4 years of follow-up, in all studied age groups.

Areas Covered: This article reviews the scientific rationale underlying the design of RZV; the clinical evidence demonstrating immunogenicity, safety, and efficacy in persons 50+; and the public health implications and cost-effectiveness.

A dynamic transmission model with age-dependent infectiousness and reactivation for cytomegalovirus in the United States: Potential impact of vaccination strategies on congenital infection.

We present an age-structured dynamic transmission model for cytomegalovirus (CMV) in the United States, based on natural history and available data, primarily aiming to combine the available qualitative and quantitative knowledge toward more complex modeling frameworks to better reflect the underlying biology and epidemiology of the CMV infection. The model structure explicitly accounts for primary infections, reactivations and re-infections. Duration of infectiousness and likelihood of reactivation were both assumed to be age-dependent, and natural reduction in the re-infection risk following primary infection was included.

Evaluation of a next generation direct whole blood enzymatic assay for hemoglobin A1c on the ARCHITECT c8000 chemistry system.

Background: The utility of HbA1c for the diagnosis of type 2 diabetes requires an accurate, precise and robust test measurement system. Currently, immunoassay and HPLC are the most popular methods for HbA1c quantification, noting however the limitations associated with some platforms, such as imprecision or interference from common hemoglobin variants. Abbott Diagnostics has introduced a fully automated direct enzymatic method for the quantification of HbA1c from whole blood on the ARCHITECT chemistry system.

A plastid DNA phylogeny of tribe Miliuseae: insights into relationships and character evolution in one of the most recalcitrant major clades of Annonaceae.

Premise Of The Study: Tribe Miliuseae (∼25 genera and ∼510 species) includes a substantial part of the species and generic diversity in the pantropical flowering-plant family Annonaceae (∼108 genera and ∼2400 species). Previous molecular phylogenetic analyses have failed to resolve the backbone phylogeny of the tribe, impeding biogeographical and evolutionary studies. We use a dense generic taxon sample (∼89% of generic diversity in Miliuseae) and plastid DNA sequence data (∼7 kb) to clarify the phylogenetic relationships of and within the tribe.

Safety and immunogenicity of an AS01-adjuvanted varicella-zoster virus subunit candidate vaccine against herpes zoster in adults >=50 years of age.

Background: An adjuvanted varicella-zoster virus glycoprotein E (gE) subunit vaccine candidate for herpes zoster is in development. In this trial we compared the safety, reactogenicity, and immunogenicity of the vaccine antigen combined with different adjuvant doses.

Methods: This was a phase II, observer-blind, randomized, multinational study.

Sampling of herpes zoster skin lesion types and the impact on viral DNA detection.

This was a multicenter, non-therapeutic study to determine the optimal type of lesion sample for quantitative PCR detection of varicella zoster virus (VZV) DNA in herpes zoster patients. Up to three crusts, three crust swabs, three vesicle swabs, and three papule swabs were collected from 41 adults with clinically diagnosed herpes zoster. 83% of subjects had at least one valid crust swab (detectable VZV or β-actin DNA), 78% had at least one valid crust, 78% had at least one valid vesicle swab, and 32% had at least one valid papule swab.

Toxicology, biodistribution and shedding profile of a recombinant measles vaccine vector expressing HIV-1 antigens, in cynomolgus macaques.

As a new human immunodeficiency virus type 1 (HIV-1) vaccine approach, the live-attenuated measles virus (MV) Schwarz vaccine strain was genetically engineered to express the F4 antigen (MV1-F4). F4 is a fusion protein comprising HIV-1 antigens p17 and p24, reverse transcriptase and Nef. This study assessed the toxicity, biodistribution and shedding profiles of MV1-F4.

One virus, one lesion--individual components of CIN lesions contain a specific HPV type.

In 20-40% of cervical intra-epithelial neoplasia (CIN) and in 4-8% of cervical carcinoma tissue specimens, multiple HPV genotypes have been detected. Whole tissue section (WTS) PCR does not determine how the individual types relate causally to complex and multiple CIN. Our objective was to determine whether laser capture micro-dissection (LCM) with HPV PCR genotyping (LCM-PCR) could accurately recover type-specific HPV DNA from epithelial cells in individual areas of CIN and normal epithelium, and whether one or more viruses are present in one lesion.

Plant protein hydrolysates support CHO-320 cells proliferation and recombinant IFN-gamma production in suspension and inside microcarriers in protein-free media.

We have recently developed a protein-free medium (PFS) able to support the growth of Chinese hamster ovary (CHO) cells in suspension. Upon further supplementation with some plant protein hydrolysates, medium performances reached what could be observed in serum-containing media [Burteau et al. In Vitro Cell.

RISC-target interaction: cleavage and translational suppression.

Small RNA molecules have been known and utilized to suppress gene expression for more than a decade. The discovery that these small RNA molecules are endogenously expressed in many organisms and have a critical role in controlling gene expression has led to the arising of a whole new field of research. Termed small interfering RNA (siRNA) or microRNA (miRNA) these approximately 22 nt RNA molecules have the capability to suppress gene expression through various mechanisms once they are incorporated in the multi-protein RNA-Induced Silencing Complex (RISC) and interact with their target mRNA.

TNF-alpha stimulation inhibits siRNA-mediated RNA interference through a mechanism involving poly-(A) tail stabilization.

The control of mRNA stability is a complex biological process that involves numerous factors, including microRNA (miRNA) and short interfering RNA (siRNA). Here, we show that short interfering RNA (siRNA) and microRNA share some similarities in their response to cellular stress. miR16 expedites the degradation of mRNAs containing AU-rich elements (ARE) in their 3' untranslated region (UTR).

Macrophage deletion of p38alpha partially impairs lipopolysaccharide-induced cellular activation.

The activation of p38alpha, a MAPK family member, is associated with macrophage activation by microbial pattern molecules, such as LPS. The requirement of p38alpha in inflammatory responses has been shown in a number of studies using chemical inhibitors, though the inhibitors also inhibit p38beta and perhaps some other enzymes. In this study, we used conditional knockout of p38alpha in macrophages to address the role of p38alpha in macrophage activation.

Hypersusceptibility to vesicular stomatitis virus infection in Dicer1-deficient mice is due to impaired miR24 and miR93 expression.

Dicer is essential for plant, Caenorhabditis elegans, and Drosophila antiviral responses because of its role in generating small interfering RNA (siRNA) from viral genomes. We show that because of impaired miRNA production, mice with a variant Dicer1 allele (Dicer1(d/d)) were more susceptible to vesicular stomatitis virus (VSV) infection. We did not detect VSV genome-derived siRNA in wild-type cells or any alteration of interferon-mediated antiviral responses by Dicer1 deficiency.

Vesicular stomatitis virus glycoprotein G activates a specific antiviral Toll-like receptor 4-dependent pathway.

We have previously shown that mutations of CD14 or TLR4 impair type I interferon (IFN) production and macrophage survival during infection with vesicular stomatitis virus (VSV). We now report that VSV glycoprotein G (gpG) is essential for the induction of a previously unrecognized CD14/TLR4-dependent response pathway in which the adapter TRAM has predominant importance, absent any need for MyD88 or Mal, and with only a partial requirement for TRIF. Downstream of TRAM, IRF7 activation leads to a type I IFN response.

Recombinant interferon-gamma secreted by Chinese hamster ovary-320 cells cultivated in suspension in protein-free media is protected against extracellular proteolysis by the expression of natural protease inhibitors and by the addition of plant protein hydrolysates to the culture medium.

Biosafety requirements increasingly restrict the cultivation of mammalian cells producing therapeutic glycoproteins to conditions that are devoid of any compound of animal origin. On cultivation in serum-free media, the proteases inhibitors, usually found in serum, cannot protect secreted recombinant proteins against unwanted endogenous proteolysis. Chinese hamster ovary (CHO) cells, secreting recombinant human interferon-gamma (CHO-320 cell line) and cultivated in suspension in an original protein-free medium, expressed at least two members of the matrix metalloproteinases (MMP), either at the cell surface (proMMP-14 and MMP-14) or secreted (proMMP-9).

Historical biogeography of two cosmopolitan families of flowering plants: Annonaceae and Rhamnaceae.

Annonaceae are a pantropically distributed family found predominantly in rainforests, so they are megathermal taxa, whereas Rhamnaceae are a cosmopolitan family that tend to be found in xeric regions and may be classified as mesothermal. Phylogenetic analyses of these families are presented based on rbcL and trnL-F plastid DNA sequences. Likelihood ratio tests revealed rate heterogeneity in both phylogenetic trees and they were therefore made ultrametric using non-parametric rate smoothing and penalized likelihood.

Origin of rice protein hydrolysates added to protein-free media alters secretion and extracellular proteolysis of recombinant interferon-gamma as well as CHO-320 cell growth.

CHO-320 cells, cultivated in suspension in a protein-free medium supplemented with rice protein hydrolysates (peptones), secrete recombinant interferon-gamma (IFN-gamma) that undergo will or will not proteolysis, depending on the origin of the peptones. This proteolytic event, as well as the appearance of an unidentified 70 kDa gelatinase-like protease, are attributed to a cysteine protease. Casein zymographies revealed that one rice protein hydrolysate, but not another, contains a papain-like cysteine protease whose activity is undetectable in solution.

Identifying clades in Asian Annonaceae: monophyletic genera in the polyphyletic Miliuseae.

The tribe Miliuseae (Annonaceae) comprises six genera distributed in Asia: Alphonsea, Mezzettia, Miliusa, Orophea, Platymitra, and Phoenicanthus. A phylogenetic study to investigate the putative monophyly of the tribe and the intergeneric relationships is presented here. Nucleotide sequences of the plastid gene rbcL, trnL intron, and trnL-trnF intergenic spacer were analyzed from 114 Annonaceae taxa, including 24 Miliuseae species and two outgroups using maximum parsimony and Bayesian inference.

Fortification of a protein-free cell culture medium with plant peptones improves cultivation and productivity of an interferon-gamma-producing CHO cell line.

A strong tendency is currently emerging to remove not only serum but also any product of animal origin from animal cell culture media during production of recombinant proteins. This should facilitate downstream processing and improve biosafety. One way consists in the fortification of protein-free nutritive media with plant protein hydrolysates.