Multivariate analyses and machine learning link sex and age with antibody responses to SARS-CoV-2 and vaccination.

Prevention of negative COVID-19 infection outcomes is associated with the quality of antibody responses, whose variance by age and sex is poorly understood. Network approaches identified sex and age effects in antibody responses and neutralization potential of infection and vaccination throughout the COVID-19 pandemic. Neutralization values followed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific receptor binding immunoglobulin G (RIgG), spike immunoglobulin G (SIgG) and spike and receptor immunoglobulin G (S, and RIgA) levels based on COVID-19 status.

Lasting differential gene expression of circulating CD8 T cells in chronic HCV infection with cirrhosis identifies a role for Hedgehog signaling in cellular hyperfunction.

Background: The impact of chronic hepatic infection on antigen non-specific immune cells in circulation remains poorly understood. We reported lasting global hyperfunction of peripheral CD8 T cells in HCV-infected individuals with cirrhosis. Whether gene expression patterns in bulk CD8 T cells are associated with the severity of liver fibrosis in HCV infection is not known.

Clinical and serological predictors of post COVID-19 condition-findings from a Canadian prospective cohort study.

Introduction: More than 3 years into the pandemic, there is persisting uncertainty as to the etiology, biomarkers, and risk factors of Post COVID-19 Condition (PCC). Serological research data remain a largely untapped resource. Few studies have investigated the potential relationships between post-acute serology and PCC, while accounting for clinical covariates.

Protocol for co-producing a framework and integrated resource platform for engaging patients in laboratory-based research.

Background: Patient engagement in research is the meaningful and collaborative interaction between patients and researchers throughout the research process. Patient engagement can help to ensure patient-oriented values and perspectives are incorporated into the development, conduct, and dissemination of research. While patient engagement is increasingly prevalent in clinical research, it remains relatively unrealized in preclinical laboratory research.

No time for complacency: The CoVaRR-Net Biobank is an essential element of laboratory preparedness for infectious disease outbreaks.

The SARS-CoV-2 pandemic highlighted the need for rapid, collaborative, and population-centric research to define health impact, develop health care policies and establish reliable diagnostic and surveillance tests. Critical for these objectives were in-depth clinical data collected in standardized fashion and large numbers of various types of human samples prior and post-viral encounter. As the pandemic evolved with the emergence of new variants of concern (VOCs), access to samples and data from infected and vaccinated individuals were needed to monitor immune durability, the possibility of increased transmissibility and virulence, and vaccine protection against new and emerging VOCs.

SARS-CoV-2 Vaccine-Induced T-Cell Response after Three Doses in People Living with HIV on Antiretroviral Therapy Compared to Seronegative Controls (CTN 328 COVAXHIV Study).

People living with HIV (PLWH) may be at risk for poor immunogenicity to certain vaccines, including the ability to develop immunological memory. Here, we assessed T-cell immunogenicity following three SARS-CoV-2 vaccine doses in PLWH versus uninfected controls. Blood was collected from 38 PLWH on antiretroviral therapy and 24 age-matched HIV-negative controls, pre-vaccination and after 1st/2nd/3rd dose of SARS-CoV-2 vaccines, without prior SARS-CoV-2 infection.

Cohort profile: top the Spread Ottawa (SSO)a community-based prospective cohort study on antibody responses, antibody neutralisation efficiency and cellular immunity to SARS-CoV-2 infection and vaccination.

Purpose: To investigate the robustness and longevity of SARS-CoV-2 immune responses conferred by natural infection and vaccination among priority populations such as immunocompromised individuals and people with post-acute sequelae of COVID-19 in a prospective cohort study (Stop the Spread Ottawa-SSO) in adults living in the Ottawa region. In this paper, we describe the study design, ongoing data collection and baseline characteristics of participants.

Participants: Since October 2020, participants who tested positive for COVID-19 (convalescents) or at high risk of exposure to the virus (under surveillance) have provided monthly blood and saliva samples over a 10-month period.

Hepatocyte-derived DPP4 regulates portal GLP-1 bioactivity, modulates glucose production, and when absent influences NAFLD progression.

Elevated circulating dipeptidyl peptidase-4 (DPP4) is a biomarker for liver disease, but its involvement in gluconeogenesis and metabolic associated fatty liver disease progression remains unclear. Here, we identified that DPP4 in hepatocytes but not TEK receptor tyrosine kinase-positive endothelial cells regulates the local bioactivity of incretin hormones and gluconeogenesis. However, the complete absence of DPP4 (Dpp4-/-) in aged mice with metabolic syndrome accelerates liver fibrosis without altering dyslipidemia and steatosis.

Longitudinal profiles of plasma gelsolin, cytokines and antibody expression predict COVID-19 severity and hospitalization outcomes.

Background: Prognostic markers for COVID-19 disease outcome are currently lacking. Plasma gelsolin (pGSN) is an actin-binding protein and an innate immune marker involved in disease pathogenesis and viral infections. Here, we demonstrate the utility of pGSN as a prognostic marker for COVID-19 disease outcome; a test performance that is significantly improved when combined with cytokines and antibodies compared to other conventional markers such as CRP and ferritin.

BATL: Bayesian annotations for targeted lipidomics.

Motivation: Bioinformatic tools capable of annotating, rapidly and reproducibly, large, targeted lipidomic datasets are limited. Specifically, few programs enable high-throughput peak assessment of liquid chromatography-electrospray ionization tandem mass spectrometry data acquired in either selected or multiple reaction monitoring modes.

Results: We present here Bayesian Annotations for Targeted Lipidomics, a Gaussian naïve Bayes classifier for targeted lipidomics that annotates peak identities according to eight features related to retention time, intensity, and peak shape.

Relative Ratios of Human Seasonal Coronavirus Antibodies Predict the Efficiency of Cross-Neutralization of SARS-CoV-2 Spike Binding to ACE2.

Background: Antibodies raised against human seasonal coronaviruses (sCoVs), which are responsible for the common cold, are known to cross-react with SARS-CoV-2 antigens. This prompts questions about their protective role against SARS-CoV-2 infections and COVID-19 severity. However, the relationship between sCoVs exposure and SARS-CoV-2 correlates of protection are not clearly identified.

TLR-4 Agonist Induces IFN-γ Production Selectively in Proinflammatory Human M1 Macrophages through the PI3K-mTOR- and JNK-MAPK-Activated p70S6K Pathway.

IFN-γ, a proinflammatory cytokine produced primarily by T cells and NK cells, activates macrophages and engages mechanisms to control pathogens. Although there is evidence of IFN-γ production by murine macrophages, IFN-γ production by normal human macrophages and their subsets remains unknown. Herein, we show that human M1 macrophages generated by IFN-γ and IL-12- and IL-18-stimulated monocyte-derived macrophages (M0) produce significant levels of IFN-γ.

The 9th Canadian Symposium on Hepatitis C Virus: Advances in HCV research and treatment towards elimination.

Hepatitis C virus (HCV) elimination has evolved into a coordinated global effort. Canada, with more than 250,000 chronically infected individuals, is among the countries leading this effort. The 9th Canadian Symposium on HCV, held in February 2020, thus established and addressed its theme, 'advances in HCV research and treatment towards elimination', by gathering together basic scientists, clinicians, epidemiologists, social scientists, and community members interested in HCV research in Canada.

Selective killing of human M1 macrophages by Smac mimetics alone and M2 macrophages by Smac mimetics and caspase inhibition.

The inflammatory and anti-inflammatory Mϕs have been implicated in many diseases including rheumatoid arthritis, multiple sclerosis, and leprosy. Recent studies suggest targeting Mϕ function and activation may represent a potential target to treat these diseases. Herein, we investigated the effect of second mitochondria-derived activator of caspases (SMAC) mimetics (SMs), the inhibitors of apoptosis (IAPs) proteins, on the killing of human pro- and anti-inflammatory Mϕ subsets.

Expression of Inhibitory Receptors on T and NK Cells Defines Immunological Phenotypes of HCV Patients with Advanced Liver Fibrosis.

Chronic HCV can result in advanced liver disease, including cirrhosis. Patients with advanced fibrosis experience poor clinical outcomes and increased risk for hepatocellular carcinoma (HCC). These outcomes are, in part, a consequence of immune dysfunction.

IL-7 induces sCD127 release and mCD127 downregulation in human CD8 T cells by distinct yet overlapping mechanisms, both of which are impaired in HIV infection.

The IL-7 receptor specific α chain, CD127, can be expressed both as a membrane-associated (mCD127) and a soluble form (sCD127), however, the mechanisms involved in their regulation remain to be defined. We first demonstrated in primary human CD8 T cells that IL-7-induced downregulation of mCD127 expression is dependent on JAK and PI3K signaling, whereas IL-7-induced sCD127 release is also mediated by STAT5. Following stimulation with IL-7, expression of alternatively spliced variants of the CD127 gene, sCD127 mRNA, is reduced, but to a lesser degree than the full-length gene.

In Vitro Hepatitis C Virus Infection and Hepatic Choline Metabolism.

Choline is an essential nutrient required for normal neuronal and muscular development, as well as homeostatic regulation of hepatic metabolism. In the liver, choline is incorporated into the main eukaryotic phospholipid, phosphatidylcholine (PC), and can enter one-carbon metabolism via mitochondrial oxidation. Hepatitis C virus (HCV) is a hepatotropic positive-strand RNA virus that similar to other positive-strand RNA viruses and can impact phospholipid metabolism.

Direct-Acting Antiviral Treatment of HCV Infection Does Not Resolve the Dysfunction of Circulating CD8 T-Cells in Advanced Liver Disease.

Chronic hepatitis C virus (HCV) infection disrupts immune functions, including that of cytotoxic CD8 T-cells which are important mediators of immune response. While HCV cure aims to eliminate long term sequelae of infection, whether direct-acting antiviral (DAA) treatment results in immune reconstitution remains unclear. We and others have reported generalized CD8 T-cell dysfunction in chronic HCV infection and our research suggests that the degree of liver damage is a factor in this process.

Chronic Hepatitis C Virus Infection Impairs M1 Macrophage Differentiation and Contributes to CD8 T-Cell Dysfunction.

Chronic hepatitis C virus (HCV) infection causes generalized CD8 T cell impairment, not limited to HCV-specific CD8 T-cells. Liver-infiltrating monocyte-derived macrophages (MDMs) contribute to the local micro-environment and can interact with and influence cells routinely trafficking through the liver, including CD8 T-cells. MDMs can be polarized into M1 (classically activated) and M2a, M2b, and M2c (alternatively activated) phenotypes that perform pro- and anti-inflammatory functions, respectively.

6th Canadian Symposium on Hepatitis C Virus: Delivering a cure for hepatitis C infection-What are the remaining gaps?

Estimates are that more than 250,000 people in Canada are chronically infected with hepatitis C virus (HCV), and many more are unaware of their infection status. If untreated, chronic HCV infection can lead to cirrhosis and subsequent complications such as hepatocellular carcinoma. The Canadian Network on Hepatitis C, supported by the Public Health Agency of Canada and the Canadian Institutes of Health Research, has been committed to the scientific study of chronic hepatitis C and to supporting the advocacy work to improve diagnosis and access to HCV care in Canada.

Hepatitis C virus core protein reduces CD8 T-cell proliferation, perforin production and degranulation but increases STAT5 activation.

Clearance of hepatitis C virus (HCV) is dependent on an effective virus-specific CD8 T-cell response, which is dysfunctional in chronic HCV infection. Dysfunction in bulk or non-HCV-specific CD8 T-cells in HCV infection has also been observed. This may contribute to observed reductions in immunity to other diseases (e.

Increased soluble IL-7 receptor concentrations associate with improved IL-7 therapy outcomes in SIV-infected ART-treated Rhesus macaques.

The use of interleukin-7 (IL-7) as an immunorestorative therapeutic has proven effective in HIV infection, cancer and bone marrow transplantation. Mediating its activity through membrane-bound IL-7 receptor α (mCD127), IL-7 therapy increases T-cell numbers and survival. A soluble form, sCD127, is found in plasma, and we have previously identified increased plasma sCD127 concentrations in HIV infection.

Generalized Liver- and Blood-Derived CD8+ T-Cell Impairment in Response to Cytokines in Chronic Hepatitis C Virus Infection.

Generalized CD8+ T-cell impairment in chronic hepatitis C virus (HCV) infection and the contribution of liver-infiltrating CD8+ T-cells to the immunopathogenesis of this infection remain poorly understood. It is hypothesized that this impairment is partially due to reduced CD8+ T-cell activity in response to cytokines such as IL-7, particularly within the liver. To investigate this, the phenotype and cytokine responsiveness of blood- and liver-derived CD8+ T-cells from healthy controls and individuals with HCV infection were compared.

Influence of female sex on hepatitis C virus infection progression and treatment outcomes.

Background: The influence of sex on hepatitis C virus (HCV)-related outcomes is often neglected. The effects of sex on liver fibrosis progression and the effect of socioeconomic status on management are unclear.

Patients And Methods: Data were evaluated from patients followed at The Ottawa Hospital and Regional Viral Hepatitis Program.

Complexed soluble IL-7 receptor α and IL-7 increase IL-7-mediated proliferation and viability of CD8⁺ T-cells in vitro.

Many soluble cytokine receptors inhibit cytokine bioactivity, while others prolong ligand activity. The biological role of an endogenous soluble form of IL-7Rα, or its therapeutic effects on CD8(+) T-cells are unknown. We demonstrate that recombinant IL-7Rα-Fc, when pre-incubated with IL-7, enhances IL-7-induced CD8(+) T-cell proliferation and viability of human or murine CD8(+) T-cells.