Biology subjects

Berrabah, W.

Publications and source records attributed to Berrabah, W..

3 recordsLinked to original sources

bioRxiv2025

Non-clinical safety of GRAd vector-based COVID-19 and HIV vaccines supports a platform regulatory approach

The rapid development of safe and efficacious vaccines is often hindered by extensive, mandated non-clinical safety evaluations in animals. Here we present the complete non-clinical studies for two investigational vaccines based on the GRAd platform, a gorilla-derived group C adenoviral vector. When administered intramuscularly, GRAd-COV2 and GRAdHIVNE1 were well tolerated. Studies in rats and rabbits showed localized distribution and transient, non-adverse inflammatory responses, while successfully inducing expected immune responses to their respective antigens. Notably, both vaccines demonstrated a consistent safety profile despite transgene and backbone differences, comparable to other replication-defective adenoviral vectors. The established non-clinical safety profile of the GRAd platform provides a robust foundation for a more efficient and streamlined regulatory pathway. By leveraging this prior knowledge, future GRAd-based vaccines can achieve accelerated clinical development while fully adhering to the ethical principles of replacement, reduction, and refinement of animal use in research.

pharmacology and toxicology↗

bioRxiv2024

Evolutionary genomics of the emergence of brown algae as key components of coastal ecosystems

Brown seaweeds are keystone species of coastal ecosystems, often forming extensive underwater forests, that are under considerable threat from climate change. Despite their ecological and evolutionary importance, this phylogenetic group, which is very distantly related to animals and land plants, is still poorly characterised at the genome level. Here we analyse 60 new genomes that include species from all the major brown algal orders. Comparative analysis of these genomes indicated the occurrence of several major events coinciding approximately with the emergence of the brown algal lineage. These included marked gain of new orthologous gene families, enhanced protein domain rearrangement, horizontal gene transfer events and the acquisition of novel signalling molecules and metabolic pathways. The latter include enzymes implicated in processes emblematic of the brown algae such as biosynthesis of the alginate-based extracellular matrix, and halogen and phlorotannin biosynthesis. These early genomic innovations enabled the adaptation of brown algae to their intertidal habitats. The subsequent diversification of the brown algal orders tended to involve loss of gene families, and genomic features were identified that correlated with the emergence of differences in life cycle strategy, flagellar structure and halogen metabolism. Analysis of microevolutionary patterns within the genus Ectocarpus indicated that deep gene flow between species may be an important factor in genome evolution on more recent timescales. Finally, we show that integration of large viral genomes has had a significant impact on brown algal genome content and propose that this process has persisted throughout the evolutionary history of the lineage.

genomics↗

bioRxiv2017

High-throughput optical mapping of replicating DNA

DNA replication is a crucial process for the universal ability of living organisms to reproduce. Existing methods to map replication genome-wide use large cell populations and therefore smooth out variability between chromosomal copies. Single-molecule methods may in principle reveal this variability. However, current methods remain refractory to automated molecule detection and measurements. Their low throughput has therefore precluded genome-wide analyses. Here, we have repurposed a commercial optical DNA mapping device, the Bionano Genomics Irys system, to map the replication signal of single DNA molecules onto genomic position at high throughput. Our methodology (HOMARD) combines fluorescent labelling of replication tracks and nicking endonuclease (NE) sites with DNA linearization in nanochannel arrays and dedicated image processing. We demonstrate the robustness of our approach by providing an ultra-high coverage (23,311 x) replication map of bacteriophage {lambda} DNA in Xenopus egg extracts. HOMARD opens the way to genome-wide analysis of DNA replication at the single-molecule level.

genomics↗