Biology subjects

Reina, G.

Publications and source records attributed to Reina, G..

3 recordsLinked to original sources

bioRxiv2026

Invisible shield: Sprayable supramolecular antimicrobial microscale films for preventing wound and medical device infections

Wound and device-associated infections remain difficult to eradicate because biofilms block host immunity and antibiotics, accelerating chronicity and resistance. Here, we present a portable, low-cost dual-syringe spray that deposits an ultra-thin, self-assembling antimicrobial film directly on wounds and implant surfaces. The device co-delivers oppositely charged hyaluronic acid (HA) and a cationic antimicrobial peptide (polyarginine, PAR30), which rapidly form a conformal nanometric polyelectrolyte complex at the tissue-material interface. Molecular dynamics simulation revealed pronounced positional heterogeneity within the PAR30/HA complex and identified an N-terminal arginine as a dominant interaction hotspot. The resulting coating adheres to diverse substrates, kills bacteria on contact, prevents biofilm formation, and sustains antimicrobial efficacy. Across vitro assays and murine wound infection models, treatment produced 4 to 5 log reductions in bacterial burden against methicillin-resistant Staphylococcus aureus and Gram-negative pathogens, including Pseudomonas aeruginosa and Escherichia coli. The formulation is biocompatible, did not increase cutaneous inflammation or IL-6 levels in vivo, and reduced post-surgical pain and motor deficits in a mouse incision model. To our knowledge, this is the first antimicrobial treatment system applicable to both tissues and medical devices. Developed under a safe-and-sustainable-by-design approach, this technology combines biocompatible components, nanometric coating for minimal material use, and a simple syringe-based delivery device, offering a scalable, antibiotic-free strategy for wound care and medical device infection prevention. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=173 HEIGHT=200 SRC="FIGDIR/small/717441v1_ufig1.gif" ALT="Figure 1"> View larger version (68K): org.highwire.dtl.DTLVardef@49381aorg.highwire.dtl.DTLVardef@1023e64org.highwire.dtl.DTLVardef@4e282aorg.highwire.dtl.DTLVardef@12eeae4_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2025

Minimal impact of ivermectin on immune response and transcriptional profiles in naïve adults with mild COVID-19

Ivermectin (IVM), an antiparasitic drug, was repurposed to treat COVID-19 based on its in vitro antiviral effects. However, it was abandoned after multiple clinical trials reported a lack of efficacy. Immunomodulatory effects have been proposed but remain unclear, yet they may be relevant given IVM use for other infections. We assessed the IVM immunomodulatory effect in 24 participants from a clinical trial evaluating its potential to reduce COVID-19 transmission in mild cases within 48 hours of symptoms onset. The IVM-treated patients showed non-significant lower viral loads, and a significantly shorter duration of hyposmia/anosmia. We measured IgG, IgA, and IgM against five SARS-CoV-2 antigens, and 30 cytokines by Luminex, alongside whole blood RNA sequencing, pan-leukocyte immunophenotyping, and SARS-CoV-2-specific T cell analysis by flow cytometry from day 1 to day 28 post-treatment. All antibody responses increased from day 4, while 13 cytokines significantly decreased over time (adjusted p<0.05). IVM-treated patients had only significantly higher anti-nucleocapsid IgG levels at day 4 (adjusted p=0.041) and 7 (adjusted p=0.045) compared to placebo. SARS-CoV-2-specific CD4+ and CD8+ T cells increased over time, with significantly higher effector memory CD4+ T cells at day 7 compared to day 1 (p=0.027) and the only difference between groups was lower frequencies of spike-specific naive CD4+ T cells at day 7 in IVM-treated participants (0.006% vs 0.036% p=0.02). Transcriptomic data showed downregulation of innate and antiviral blood transcriptional modules (BTMs) over time, with an increase in adaptive immune related BTMs. While no differential gene expression was detected, the IVM-treated had upregulated innate and downregulated T cell and cell cycle BTMs compared to placebo. Overall, our comprehensive longitudinal analysis of early immune responses in mild COVID-19 revealed no robust immunological effects of IVM, consistent with clinical trials results and suggesting a lack of efficacy of IVM in COVID-19 treatment. AUTHOR SUMMARYIvermectin (IVM), an antiparasitic drug, was tested in clinical trials as a potential treatment for COVID-19 due to its in vitro antiviral properties and hypothetical immunomodulatory effects. In this study, we explored the immunomodulatory effects of IVM in a clinical trial involving 24 mild COVID-19 patients who received IVM within 48 hours of symptoms onset. The IVM group showed a trend towards lower viral loads post-treatment, and a significantly shorter duration of hyposmia/anosmia. We comprehensively analyzed immune responses by measuring antibody levels, cytokine profiles, immune cell subsets and whole blood gene expression over 28 days. The IVM group only had increased levels of IgG against the SARS-CoV-2 nucleocapsid compared to the control group. IVM did not affect the kinetics of SARS-CoV-2 T cells, despite a slight decrease in naive CD4+ T cells. Additionally, gene expression analysis showed a decrease in innate and antiviral responses and an increase of adaptive responses over time that were slightly stronger in the placebo compared to the IVM group. In conclusion, despite some differences in IVM treated participants, our detailed analyses do not support significant immunomodulatory effects that could benefit disease progression.

immunology↗

bioRxiv2020

Highly sensitive and specific multiplex antibody assays to quantify immunoglobulins M, A and G against SARS-CoV-2 antigens

Reliable serological tests are required to determine the prevalence of antibodies against SARS-CoV-2 antigens and to characterise immunity to the disease in order to address key knowledge gaps in the context of the COVID-19 pandemic. Quantitative suspension array technology (qSAT) assays based on the xMAP Luminex platform overcome the limitations of rapid diagnostic tests and ELISA with their higher precision, dynamic range, throughput, miniaturization, cost-efficacy and multiplexing capacity. We developed three qSAT assays to detect IgM, IgA and IgG to a panel of eight SARS-CoV-2 antigens including spike (S), nucleoprotein (N) and membrane (M) protein constructs. The assays were optimized to minimize processing time and maximize signal to noise ratio. We evaluated the performance of the assays using 128 plasmas obtained before the COVID-19 pandemic (negative controls) and 115 plasmas from individuals with SARS-CoV-2 diagnosis (positive controls), of whom 8 were asymptomatic, 58 had mild symptoms and 49 were hospitalized. Pre-existing IgG antibodies recognizing N, M and S2 proteins were detected in negative controls suggestive of cross-reactive to common cold coronaviruses. The best performing antibody isotype/antigen signatures had specificities of 100% and sensitivities of 94.94% at [≥]14 days since the onset of symptoms and 96.08% at [≥]21 days since the onset of symptoms, with AUC of 0.992 and 0.999, respectively. Combining multiple antibody markers as assessed by qSAT assays has the highest efficiency, breadth and versatility to accurately detect low-level antibody responses for obtaining reliable data on prevalence of exposure to novel pathogens in a population. Our assays will allow gaining insights into antibody correlates of immunity required for vaccine development to combat pandemics like the COVID-19.

immunology↗