An integrative network-based approach to identify driving gene communities in chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is an etiologically complex disease characterized by acute exacerbations and stable phases. We aimed to identify biological functions modulated in specific COPD conditions, using whole blood samples collected in the AERIS clinical study (NCT01360398). Considered conditions were exacerbation onset, severity of airway obstruction, and presence of respiratory pathogens in sputum samples.

4CMenB journey to the 10-year anniversary and beyond.

The 4-component meningococcal serogroup B (MenB) vaccine, 4CMenB, the first broadly protective, protein-based MenB vaccine to be licensed, is now registered in more than 50 countries worldwide. Real-world evidence (RWE) from the last decade confirms its effectiveness and impact, with infant immunization programs showing vaccine effectiveness of 71-95% against invasive MenB disease and cross-protection against non-B serogroups, including a 69% decrease in serogroup W cases in 4CMenB-eligible cohorts in England. RWE from different countries also demonstrates the potential for additional moderate protection against gonorrhea in adolescents.

Prediction by genetic MATS of 4CMenB vaccine strain coverage of invasive meningococcal serogroup B isolates circulating in Taiwan between 2003 and 2020.

serogroup B (NmB) strains have diverse antigens, necessitating methods for predicting meningococcal serogroup B (MenB) vaccine strain coverage. The genetic Meningococcal Antigen Typing System (gMATS), a correlate of MATS estimates, predicts strain coverage by the 4-component MenB (4CMenB) vaccine in cultivable and non-cultivable NmB isolates. In Taiwan, 134 invasive, disease-causing NmB isolates were collected in 2003-2020 (23.

Ex-vivo RNA expression analysis of vaccine candidate genes in COPD sputum samples.

Background: Chronic obstructive pulmonary disease (COPD) is a lung disease characterised by airflow-limiting inflammation and mucus production. Acute exacerbations are a major cause of COPD-related morbidity and mortality and are mostly associated with bacterial or viral infections. A vaccine targeting non-typeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis (Mcat), the main bacteria associated with exacerbations, was tested in a Phase 2 trial.

Use of expanded serogroup B panels with the serum bactericidal antibody assay for the evaluation of meningococcal B vaccine effectiveness.

Introduction: serogroup B (NmB) antigens are inherently diverse with variable expression among strains. Prediction of meningococcal B (MenB) vaccine effectiveness therefore requires an assay suitable for use against large panels of epidemiologically representative disease-causing NmB strains. Traditional serum bactericidal antibody assay using exogenous human complement (hSBA) is limited to the quantification of MenB vaccine immunogenicity on a small number of indicator strains.

OpcA and PorB are novel bactericidal antigens of the 4CMenB vaccine in mice and humans.

The ability of Neisseria meningitidis Outer Membrane Vesicles (OMV) to induce protective responses in humans is well established and mainly attributed to Porin A (PorA). However, the contribution of additional protein antigens to protection remains to be elucidated. In this study we dissected the immunogenicity of antigens originating from the OMV component of the 4CMenB vaccine in mice and humans.

Genetic Features of a Representative Panel of 110 Meningococcal B Isolates to Assess the Efficacy of Meningococcal B Vaccines.

Predictions of vaccine efficacy against Neisseria meningitidis serogroup B (NmB) disease are hindered by antigenic variability, limiting the representativeness of individual NmB isolates. A qualitative human serum bactericidal assay using endogenous complements of individual subjects (enc-hSBA) enables large panels of NmB isolates to be tested. A 110-isolate panel was randomly selected from 442 invasive NmB isolates from United States cases reported to the Centers for Disease Control (CDC) from 2000 to 2008.

Evolution of strain coverage by the multicomponent meningococcal serogroup B vaccine (4CMenB) in France.

The 4CMenB, a protein-based vaccine, was licensed in Europe in 2013 against invasive meningococcal disease caused by serogroup B and is currently implemented in several countries although according to different national strategies. Isolate coverage estimation is required as vaccine-targeted antigens may vary among isolates over time. Several phenotypic and genotypic methods have been developed to predict strain coverage by scoring the expression and cross-reactivity of vaccine antigens using the Meningococcal Antigen Typing system (MATS), by the genetic correlation of alleles encoding these antigens and MATS expression data (gMATS) and by the Meningococcal Deduced Vaccine Antigen Reactivity (MenDeVAR).

Dissecting the Human Response to Systemic Infections.

is a common human commensal and the leading cause of diverse infections. To identify distinctive parameters associated with infection and colonization, we compared the immune and inflammatory responses of patients with a diagnosis of invasive disease to healthy donors. We analyzed the inflammatory responses founding a pattern of distinctive cytokines significantly higher in the patients with invasive disease.

High coverage of diverse invasive meningococcal serogroup B strains by the 4-component vaccine 4CMenB in Australia, 2007-2011: Concordant predictions between MATS and genetic MATS.

Meningococcal serogroup B (MenB) accounts for an important proportion of invasive meningococcal disease (IMD). The 4-component vaccine against MenB (4CMenB) is composed of factor H binding protein (fHbp), neisserial heparin-binding antigen (NHBA), adhesin A (NadA), and outer membrane vesicles of the New Zealand strain with Porin 1.4.

Deconvolution of intergenic polymorphisms determining high expression of Factor H binding protein in meningococcus and their association with invasive disease.

Neisseria meningitidis is a strictly human pathogen and is the major cause of septicemia and meningitis worldwide. Factor H binding protein (fHbp) is a meningococcal surface-exposed lipoprotein that binds the human Complement factor H allowing the bacterium to evade the host innate immune response. FHbp is also a key antigen in two vaccines against N.

Genomic Characterization of Invasive Meningococcal Serogroup B Isolates and Estimation of 4CMenB Vaccine Coverage in Finland.

Invasive meningococcal disease (IMD) caused by is a significant cause of morbidity and mortality worldwide. In Finland, the incidence rate of IMD is low, with meningococcal serogroup B (MenB) accounting for around one-third of IMD cases annually. The aim of this study was to investigate the genetic variability of invasive MenB isolates collected in Finland between 2010 and 2017 ( = 81), including the genes encoding the 4-component MenB vaccine (4CMenB; Bexsero; GSK) antigens and their promoters, and to evaluate the 4CMenB potential coverage.

The global meningitis genome partnership.

Genomic surveillance of bacterial meningitis pathogens is essential for effective disease control globally, enabling identification of emerging and expanding strains and consequent public health interventions. While there has been a rise in the use of whole genome sequencing, this has been driven predominately by a subset of countries with adequate capacity and resources. Global capacity to participate in surveillance needs to be expanded, particularly in low and middle-income countries with high disease burdens.

STRAIN: an R package for multi-locus sequence typing from whole genome sequencing data.

Background: Multi-locus sequence typing (MLST) is a standard typing technique used to associate a sequence type (ST) to a bacterial isolate. When the output of whole genome sequencing (WGS) of a sample is available the ST can be assigned directly processing the read-set. Current approaches employ reads mapping (SRST2) against the MLST loci, k-mer distribution (stringMLST), selective assembly (GRAbB) or whole genome assembly (BIGSdb) followed by BLASTn sequence query.

Genetic Meningococcal Antigen Typing System (gMATS): A genotyping tool that predicts 4CMenB strain coverage worldwide.

Background: The Meningococcal Antigen Typing System (MATS) was developed to identify meningococcus group B strains with a high likelihood of being covered by the 4CMenB vaccine, but is limited by the requirement for viable isolates from culture-confirmed cases. We examined if antigen genotyping could complement MATS in predicting strain coverage by the 4CMenB vaccine.

Methods: From a panel of 3912 MATS-typed invasive meningococcal disease isolates collected in England and Wales in 2007-2008, 2014-2015 and 2015-2016, and in 16 other countries in 2000-2015, 3481 isolates were also characterized by antigen genotyping.

A Pipeline for the Analysis of High Density Arrays of Bacterial Transcriptomes.

is a pipeline for bacterial transcriptome studies based on high-density microarray experiments. The main algorithm , integrates the analysis of the hybridization signal with the genomic position of probes and identifies portions of the genome transcribing for mRNAs. The pipeline includes a procedure, , to build a multiple alignment of transcripts originating in the same locus in multiple experiments and provides a method to compare mRNA expression across different conditions.

Predicted Strain Coverage of a New Meningococcal Multicomponent Vaccine (4CMenB) in Spain: Analysis of the Differences with Other European Countries.

Background: A novel meningococcal multicomponent vaccine, 4CMenB (Bexsero®), has been approved in Europe, Canada, Australia and US. The potential impact of 4CMenB on strain coverage is being estimated by using Meningococcal Antigen Typing System (MATS), an ELISA assay which measures vaccine antigen expression and diversity in each strain. Here we show the genetic characterization and the 4CMenB potential coverage of Spanish invasive strains (collected during one epidemiological year) compared to other European countries and discuss the potential reasons for the lower estimate of coverage in Spain.

Expression of factor H binding protein in meningococcal strains can vary at least 15-fold and is genetically determined.

Factor H binding protein (fHbp) is a lipoprotein of Neisseria meningitidis important for the survival of the bacterium in human blood and a component of two recently licensed vaccines against serogroup B meningococcus (MenB). Based on 866 different amino acid sequences this protein is divided into three variants or two families. Quantification of the protein is done by immunoassays such as ELISA or FACS that are susceptible to the sequence variation and expression level of the protein.

Dual RNA-seq of Nontypeable Haemophilus influenzae and Host Cell Transcriptomes Reveals Novel Insights into Host-Pathogen Cross Talk.

Unlabelled: The ability to adhere and adapt to the human respiratory tract mucosa plays a pivotal role in the pathogenic lifestyle of nontypeable Haemophilus influenzae (NTHi). However, the temporal events associated with a successful colonization have not been fully characterized. In this study, by reconstituting the ciliated human bronchial epithelium in vitro, we monitored the global transcriptional changes in NTHi and infected mucosal epithelium simultaneously for up to 72 h by dual RNA sequencing.

Global transcriptome analysis reveals small RNAs affecting Neisseria meningitidis bacteremia.

Most bacterial small RNAs (sRNAs) are post-transcriptional regulators involved in adaptive responses, controlling gene expression by modulating translation or stability of their target mRNAs often in concert with the RNA chaperone Hfq. Neisseria meningitides, the leading cause of bacterial meningitis, is able to adapt to different host niches during human infection. However, only a few sRNAs and their functions have been fully described to date.

Whole-Genome Sequences of Nonencapsulated Haemophilus influenzae Strains Isolated in Italy.

Haemophilus influenzae is an important human pathogen involved in invasive disease. Here, we report the whole-genome sequences of 11 nonencapsulated H. influenzae (ncHi) strains isolated from both invasive disease and healthy carriers in Italy.