When to update COVID-19 vaccine composition

Vaccines against different SARS-CoV-2 variants have been approved, but continued surveillance is needed to determine when the antigen composition of vaccines should be updated, together with clinical studies to assess vaccine efficacy

Cellular biology, genetics and genomics : A powerful liaison to reveal genotype phenotype correlations

This study integrates multiple recent concepts and technologies to address a major aim in medical genetics: identifying susceptibility loci for complex diseases, including Trisomy 21. In particular, we establish a category of quantitative cellular phenotypes that are closely linked to clinical manifestations and perform genome-wide linkage and association studies to detect regulatory loci Chapter I describes the set-up of an experimental protocol to measure a cellular phenotype in large population sizes. We choose to investigate reactive oxygen species (ROS) production as a fundamental cellular signaling phenotype related to the innate immune system that may be involved in clinical manifestations of Down syndrome patients. Chapter II and III investigate the gentics and the biological significance of phenotypic natural variation, both in cellular phenotypes and in gene expression levels. Both studies aim at identifying loci that regulate the correlations between genetic and natural phenotypic variation in human cell lines of several cohorts

Burden of endemic health-care-associated infection in developing countries: systematic review and meta-analysis

Health-care-associated infection is the most frequent result of unsafe patient care worldwide, but few data are available from the developing world. We aimed to assess the epidemiology of endemic health-care-associated infection in developing countries

Three common polymorphisms in the CYBA gene form a haplotype associated with decreased ROS generation

NOX enzymes are reactive oxygen species (ROS)-generating NADPH oxidases. Several members of the NOX family depend on the p22(phox) subunit, encoded by the CYBA gene. CYBA is highly polymorphic, and has been widely studied as a potential risk factor for various diseases, with conflicting results. In the present study, we used Epstein-Barr (EBV)-transformed B-lymphocytes from 50 healthy unrelated individuals to analyze their CYBA mRNA sequence and NOX2-dependent ROS generation. Seven single-nucleotide polymorphisms (SNPs) were identified (five previously described, two novel). The combination of these SNPs yielded 11 distinct haplotypes, which could be grouped into seven haplogroups (A-G). Haplogroup C (c.214T>C, c.521T>C, and c.(*)24G>A) showed a significantly lower ROS generation, as compared to the most frequent haplogroup, A. CYBA variants from the seven haplogroups were transduced into p22(phox)-deficient B-lymphocytes. The haplogroup C variant showed significantly lower ROS production. c.214T>C and c.521T>C lead to nonsynonymous codon changes, while c.(*)24G>A lies within the 3'UTR. Using a luciferase/3'UTR construct, we showed that the (*)24A allele led to decreased reporter gene activity. These results help to unravel the complex nature of how genetic variations in CYBA influence NOX2 activity, and indicate that haplotypes, rather than individual SNPs, define the effect on ROS generation

Common regulatory variation impacts gene expression in a cell type-dependent manner

Studies correlating genetic variation to gene expression facilitate the interpretation of common human phenotypes and disease. As functional variants may be operating in a tissue-dependent manner, we performed gene expression profiling and association with genetic variants (single-nucleotide polymorphisms) on three cell types of 75 individuals. We detected cell type-specific genetic effects, with 69 to 80% of regulatory variants operating in a cell type-specific manner, and identified multiple expressive quantitative trait loci (eQTLs) per gene, unique or shared among cell types and positively correlated with the number of transcripts per gene. Cell type-specific eQTLs were found at larger distances from genes and at lower effect size, similar to known enhancers. These data suggest that the complete regulatory variant repertoire can only be uncovered in the context of cell-type specificity

When to update COVID-19 vaccine composition

Entering the fourth year of the COVID-19 pandemic, index virus-based1 vaccines across several different platforms continue to provide high levels of protection against severe disease caused by all variants of SARS-CoV-2, including Omicron2. However, there has been continuous and substantial evolution of SARS-CoV-2 since the virus emerged, posing challenges to the ongoing public health response, including ensuring that vaccines continue to provide protection. In September 2021, the World Health Organization (WHO) established the Technical Advisory Group on COVID-19 Vaccine Composition (TAG-CO-VAC)3 to assess the public health implications of emerging SARS-CoV-2 variants of concern (VOC) on the performance of COVID-19 vaccines and to issue timely recommendations on proposed modifications to vaccine antigen composition. The TAG-CO-VAC has evaluated evidence to inform its advice on COVID-19 vaccine composition so far, but there remain challenges and evidence gaps that the scientific community needs to address to enable future, timely decisions on modifications to COVID-19 vaccine antigen composition

An updated framework for SARS-CoV-2 variants reflects the unpredictability of viral evolution

The World Health Organization framework for tracking SARS-CoV-2 variants has been updated to reflect the continued evolution of the virus; this framework could be adapted for other emerging respiratory diseases with epidemic and pandemic potential

An updated framework for SARS-CoV-2 variants reflects the unpredictability of viral evolution

The World Health Organization framework for tracking SARS-CoV-2 variants has been updated to reflect the continued evolution of the virus; this framework could be adapted for other emerging respiratory diseases with epidemic and pandemic potential

An early warning system for emerging SARS-CoV-2 variants.

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