Biology subjects

Glanville, J.

Publications and source records attributed to Glanville, J..

6 recordsLinked to original sources

bioRxiv2026

Rapid in vitro synthesis of DNA templates via Sidewinder for polyadenylated Hantavirus mRNA vaccine candidates

As the recent COVID-19 pandemic illustrated, zoonotic viruses and other pathogens pose a credible threat to public health. Recent advancements in vaccine technology, particularly mRNA vaccines, provide key tools for an effective and swift public health response. Although mRNA vaccines can be developed more quickly than traditional vaccines, fast and accurate construction of DNA templates for these vaccines remains a critical bottleneck. Using our novel DNA assembly technology, Sidewinder, we rapidly designed and built multiple mRNA vaccine candidates to guard against a potential outbreak of Hantavirus (ANDV). We successfully constructed the DNA templates from oligo pools and produced the mRNA for three vaccine candidates in just 2 days after delivery of the synthetic DNA oligos.

biochemistry↗

bioRxiv2025

Relationship between SARC-F score and Peripheral Blood Lymphocytes in Juvenile Idiopathic Arthritis: An Observational Pilot Study

BackgroundGiven the relatively high prevalence of sarcopenia and immune profile abnormalities in inflammatory arthritis such as rheumatoid arthritis (RA), we investigated the relationship between exercise habits, SARC-F score and peripheral blood lymphocyte profiles in patients with Juvenile idiopathic arthritis (JIA). MethodsAll participants with JIA completed the SARC-F survey and self-reported exercise habits through online questionnaires. We defined two groups based on SARC-F scores as musculoskeletal function impaired (SARC-Fhi+) and musculoskeletal function not impaired (SARC-Fhi-). We used flow cytometry of peripheral blood mononuclear cells to define immune cell subpopulations. Statistical analyses were performed using GraphPad Prism software version10. ResultsOf the 18 participants with a median age of 24 years - five belonged to the SARC-Fhi+ group and 13 to the SARC-Fhi-group, of whom 80% and 38% were female, respectively. The SARC-Fhi + group had fewer CD45RA+CD27+ naive CD4+ T cells (26.60% vs. 45.30%, p=0.0264) and greater CD45RA-CD27-effector memory CD4+ T cells (11.90% vs. 7.00%, p=0.0350). The SARC-Fhi+ group also had fewer CD56-CD16+ NK cells compared to the SARC-Fhi-group (2.60% v. 4.28%, p = 0.0194). The moderate exercise group (n = 13) had increased numbers of total CD4+ T cells (54.06% vs. 37.30%, p=0.0140) and 3-fold fewer CD45RA+CD27-EMRA CD8+ T cells (3.17% vs. 10.40%, p=0.0350). There were no other significant differences for other immune cells / subpopulations including B cells. ConclusionsOur study findings suggest notable differences in immune profile relative to SARC-F score. Furthermore, the 3-fold lower frequency of CD8+ TEMRA subpopulation of T cells, reflective of immunosenescence, suggest a potential inverse relationship between moderate exercise and peripheral immune cell profile in JIA. Key messagesO_LISARC-F score was used as a clinically relevant tool to identify musculoskeletal function in JIA C_LIO_LISARC-Fhi+ group had fewer naive CD4+ T cells and greater effector memory CD4+ T cells C_LIO_LIModerate exercise group had 3-fold lower frequency of CD8+ TEMRA T cells C_LI Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=54 SRC="FIGDIR/small/681879v1_ufig1.gif" ALT="Figure 1"> View larger version (11K): org.highwire.dtl.DTLVardef@1eb9d4org.highwire.dtl.DTLVardef@13a18a4org.highwire.dtl.DTLVardef@127d55corg.highwire.dtl.DTLVardef@28bddf_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2022

Venom protection by antibody from a snakebite hyperimmune subject

Snake envenomation is a neglected tropical disease, causing >100,000 deaths and 300,000 permanent disabilities in humans annually. Could monoclonal antibody technology provide a solution? Here, we recover Centi-3FTX-D09, a potent broadly neutralizing antivenom antibody from the B-cell memory of a human subject with snake venom exposure. Centi-3FTX-D09 recognized a conserved neutralizing epitope on long 3-finger toxins (3FTXs), a dominant snake neurotoxin. Crystal structures of Centi-3FTX-D09 in complex with 3FTXs from mamba, taipan, krait, and cobra revealed epitope mimicry of the interface between these neurotoxins and their host target, the nicotinic acetylcholine receptor. Centi-3FTX-D09 provided in-vivo protection against diverse recombinant long 3FTXs, in-vivo rescue from whole venom challenge from cobras, black mamba, and king cobra, and, when combined with the phospholipase inhibitor varespladib, in-vivo protection extending to a majority of tested elapid venoms. Thus, a single antibody can broadly neutralize long neurotoxins and contribute to broad protection from envenomation.

immunology↗

bioRxiv2020

Multivalency transforms SARS-CoV-2 antibodies into broad and ultrapotent neutralizers

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes Coronavirus Disease 2019 (COVID-19), has caused a global pandemic. Antibodies are powerful biotherapeutics to fight viral infections; however, discovery of the most potent and broadly acting clones can be lengthy. Here, we used the human apoferritin protomer as a modular subunit to drive oligomerization of antibody fragments and transform antibodies targeting SARS-CoV-2 into exceptionally potent neutralizers. Using this platform, half-maximal inhibitory concentration (IC50) values as low as 9 x 10-14 M were achieved as a result of up to 10,000-fold potency enhancements. Combination of three different antibody specificities and the fragment crystallizable (Fc) domain on a single multivalent molecule conferred the ability to overcome viral sequence variability together with outstanding potency and Ig-like in vivo bioavailability. This MULTi-specific, multi-Affinity antiBODY (Multabody; or MB) platform contributes a new class of medical countermeasures against COVID-19 and an efficient approach to rapidly deploy potent and broadly-acting therapeutics against infectious diseases of global health importance. One Sentence Summarymultimerization platform transforms antibodies emerging from discovery screens into potent neutralizers that can overcome SARS-CoV-2 sequence diversity.

molecular biology↗

bioRxiv2020

Disruption of Adaptive Immunity Enhances Disease in SARS-CoV-2 Infected Syrian Hamsters

Animal models recapitulating human COVID-19 disease, especially with severe disease, are urgently needed to understand pathogenesis and evaluate candidate vaccines and therapeutics. Here, we develop novel severe disease animal models for COVID-19 involving disruption of adaptive immunity in Syrian hamsters. Cyclophosphamide (CyP) immunosuppressed or RAG2 knockout (KO) hamsters were exposed to SARS-CoV-2 by the respiratory route. Both the CyP-treated and RAG2 KO hamsters developed clinical signs of disease that were more severe than in immunocompetent hamsters, notably weight loss, viral loads, and fatality (RAG2 KO only). Disease was prolonged in transiently immunosuppressed hamsters and uniformly lethal in RAG2 KO hamsters. We evaluated the protective efficacy of a neutralizing monoclonal antibody and found that pretreatment, even in immunosuppressed animals, limited infection. Our results suggest that functional B and/or T cells are not only important for the clearance of SARS-CoV-2, but also play an early role in protection from acute disease. One Sentence SummaryAn antibody targeting the spike protein of SARS-CoV-2 limits infection in immunosuppressed Syrian hamster models.

microbiology↗

bioRxiv2020

Monocyte-derived Prostaglandin E2 inhibits antigen-specific cutaneous immunity during ageing

Ageing results in a decline in immune function. We showed previously that healthy older humans (>65 years old) have reduced antigen-specific cutaneous immunity to varicella zoster virus (VZV) antigen challenge. This was associated with p38 MAP kinase driven inflammation that was induced by mild tissue injury caused by the injection of the antigen itself. Here we show that non-specific injury induced by injection of air or saline into the skin of older adults recruits CCR2+CD14+ monocytes by CCL2 produced by senescent fibroblasts. These monocytes reduced TRM proliferation via secretion of prostaglandin E2 (PGE2). Pre-treatment with a p38-MAPK inhibitor (Losmapimod) in older adults in vivo significantly decreased CCL2 expression, recruitment of monocyte into the skin, COX2 expression and PGE2 production. This enhanced the VZV response in the skin. Therefore, local inflammation arising from interaction between senescent cells and monocytes leads to immune decline in the skin during ageing, a process that can be reversed. SummaryInflammation resulting from tissue injury blocks antigen-specific cutaneous immunity during ageing. Monocytes recruited to the skin inhibit TRM function through COX2-derived prostaglandin E2 production. Blocking inflammation and resulting prostaglandin E2 production with a p38-MAP kinase inhibitor significantly enhances cutaneous antigen-specific responses.

immunology↗