Genova, C. | bioRxiv Science

bioRxiv2026

Tools for genetic mapping and gene identification in Caenorhabditis briggsae

The nematode Caenorhabditis briggsae serves as an important companion species for Caenorhabditis elegans for comparative studies. Because C. briggsae exhibits androdioecious reproduction and ease of laboratory culture similar to C. elegans, it has long been used for genetic studies in cross-species comparisons of mutant phenotypes to uncover the evolution of gene function. Here, we provide an updated toolkit for C. briggsae genetic experiments, leveraging the resource of recently improved C. briggsae genome sequence assemblies with variant mapping tools and gene identification methods. We identify and validate a set of indel variants between CGC2 (AF16) and two divergent strains, HK104 and VX34. We then use these variants to genetically map 10 previously isolated mutations and identify the impacted genes using high-throughput sequencing. We combine these new genes with others curated from the literature into an updated map with 73 genes, providing an enriched resource for C. briggsae genetic studies.

genetics↗

bioRxiv2024

Biological modifications of the immune response to COVID-19 vaccine in patients treated with anti-CD20 agents and immune-checkpoint inhibitors

Investigating the impact of immune-modulating therapies on mRNA vaccine efficacy transcends the immediate context of the COVID-19 pandemic. This study focuses on the differential immune responses to the third dose of COVID-19 mRNA vaccine among healthy volunteers, cancer patients treated with immune-checkpoint inhibitors (ICIs), and those treated with the anti-CD20 antibody rituximab. Utilizing RNA sequencing, serology, and interferon-{gamma} release assessment, we charted the temporal dynamics of the immune response in such cohorts. Our findings indicate that ICIs maintain an immune profile similar to that of healthy individuals, whereas treatment with rituximab is associated with impairment of type I interferon response and the upregulation of transcripts pertaining to regulatory T cells, with a global dysfunction of both humoral and cellular immunity. This research deepens our understanding of the sophisticated interplay within the immune system in health and disease states, potentially informing therapeutic strategies across a spectrum of immunological conditions. Significance statementOur study examines how cancer treatments that modify the immune system affect transcriptional, serological, and cellular responses to a model for repeated antigenic stimulation in humans, represented by the SARS-CoV-2 booster vaccine. Specifically, we investigated patients treated with rituximab (RTX), which impairs antibody production, and immune checkpoint inhibitors (ICI), which can trigger autoimmune disorders. We discovered that RTX-treated patients not only exhibit a reduced antibody response but actually show a diminished interferon-mediated immune response, indicating a broader immune disruption than anticipated. Conversely, ICI-treated patients responded to the vaccine similarly to healthy individuals, suggesting that fears of adverse vaccine reactions in these patients may be unfounded. This research highlights important considerations for the clinical management of cancer patients receiving these treatments.

immunology↗