A5066625736- SARS-CoV-2 and COVID-19 Research
- Influenza Virus Research Studies
- Respiratory viral infections research
- SARS-CoV-2 detection and testing
- COVID-19 Clinical Research Studies
- Immune Cell Function and Interaction
- COVID-19 epidemiological studies
- Monoclonal and Polyclonal Antibodies Research
- Immune Response and Inflammation
- Advanced biosensing and bioanalysis techniques
- Vaccine Coverage and Hesitancy
- interferon and immune responses
- Viral gastroenteritis research and epidemiology
- Cytomegalovirus and herpesvirus research
- Herpesvirus Infections and Treatments
- Advanced Combinatorial Mathematics
- Immunotherapy and Immune Responses
- Organ Donation and Transplantation
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Virus-based gene therapy research
- Neuroscience and Neuropharmacology Research
- Bacteriophages and microbial interactions
- Animal Virus Infections Studies
- Diabetes and associated disorders
- Immune responses and vaccinations
McMaster University Medical Centre
2016-2025
McMaster University
2015-2025
St. Joseph’s Healthcare Hamilton
2018-2025
The University of Texas at Austin
2020-2023
The University of Texas Medical Branch at Galveston
2023
John Sealy Hospital
2023
Mount Sinai Hospital
2020
University of Toronto
2020
Sunnybrook Hospital
2020
Sunnybrook Research Institute
2020
The emerging SARS-CoV-2 variants of concern (VOCs) threaten the effectiveness current COVID-19 vaccines administered intramuscularly and designed to only target spike protein. There is a pressing need develop next-generation vaccine strategies for broader long-lasting protection. Using adenoviral vectors (Ad) human chimpanzee origin, we evaluated Ad-vectored trivalent expressing spike-1, nucleocapsid, RdRp antigens in murine models. We show that single-dose intranasal immunization,...
HighlightsAntibodies against SARS-CoV-2 Spike correlate with COVID-19 severityRBD-specific IgM and IgA decline more rapidly than IgGSARS-CoV-2 neutralizing antibodies are elicited within 2 weeks of infectionNeutralizing significantly after resolution the infectionSummarySARS-CoV-2 is responsible for coronavirus disease 2019 (COVID-19) pandemic, infecting millions people causing hundreds thousands deaths. The glycoproteins mediate viral entry main targets antibodies. Understanding antibody...
Significance Vaccination is the most effective means of attaining protection against influenza viruses. However, constantly evolving nature viruses enables them to escape preexisting immune surveillance, and thus thwarts public health efforts control annual epidemics occasional pandemics. One solution elicit antibodies directed highly conserved epitopes, such as those within stem region HA, principal target virus-neutralizing antibody responses. This study shows that vaccines induce...
The generation of strain-specific neutralizing antibodies against influenza A virus is known to confer potent protection homologous infections. majority these bind the hemagglutinin (HA) head domain and function by blocking receptor binding site, preventing infection host cells. Recently, elicitation broadly which target conserved HA stalk has become a promising "universal" vaccine strategy. ability elicit Fc-dependent effector functions emerged as an important mechanism through achieved in...
In December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged, causing the disease 2019 (COVID-19) pandemic. SARS-CoV, agent responsible for 2003 SARS outbreak, utilises angiotensin-converting enzyme (ACE2) and transmembrane serine protease (TMPRSS2) host molecules viral entry. ACE2 TMPRSS2 have recently been implicated in SARS-CoV-2 infection. Additional including ADAM17, cathepsin L, CD147 GRP78 may also function as receptors SARS-CoV-2.To determine expression
We report a simple and rapid saliva-based SARS-CoV-2 antigen test that utilizes newly developed dimeric DNA aptamer, denoted as DSA1N5, specifically recognizes the spike proteins of wildtype virus its Alpha Delta variants with dissociation constants 120, 290 480 pM, respectively, binds pseudotyped lentiviruses expressing alpha trimeric affinity 2.1 pM 2.3 respectively. To develop highly sensitive test, DSA1N5 was immobilized onto gold electrodes to produce an electrochemical impedance...
We performed in vitro selection experiments to identify DNA aptamers for the S1 subunit of SARS-CoV-2 spike protein (S1 protein). Using a pool pre-structured random sequences, we obtained over 100 candidate after 13 cycles enrichment under progressively more stringent pressure. The top 10 sequences all exhibited strong binding protein. Two aptamers, named MSA1 (Kd = 1.8 nM) and MSA5 2.7 nM), were assessed heat-treated protein, untreated spiked into 50% human saliva trimeric both wildtype...
We have identified a bis-ethylthiomethyl analog of K-252a, CEP-1347/KT-7515, that promotes neuronal survival in culture and vivo. The properties CEP-1347/KT-7515 may be related to its ability inhibit the activation c-jun N-terminal kinase, key kinase some forms stress-induced death perhaps apoptosis. There is evidence selective nigrostriatal dopaminergic neurotoxin, MPTP, produces apoptosis adult mice. Thus, our studies were designed determine if could protect neurons from MPTP-mediated...
Antigenic variation promotes neutralizing antibodies to both seasonal and pandemic influenza A strains in humans.
The worldwide spread of a novel influenza A (H1N1) virus in 2009 showed that remains significant health threat, even for individuals the prime life. This paper focuses on unusually high young adult mortality observed during Spanish flu pandemic 1918. Using historical records from Canada and U.S., we report peak at exact age 28 argue this increased resulted an early life exposure to previous Russian 1889–90. We posit specific instances, development immunological memory strain may lead...
Abstract The aim of candidate universal influenza vaccines is to provide broad protection against A and B viruses. Studies have demonstrated that broadly reactive antibodies require Fc–Fc gamma receptor interactions for optimal protection; however, the innate effector cells responsible mediating this remain largely unknown. Here, we examine roles alveolar macrophages, natural killer cells, neutrophils in antibody-mediated protection. We demonstrate macrophages play a dominant role conferring...
Since its emergence in Wuhan, China, December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected ≈6 million persons worldwide. As SARS-CoV-2 spreads across the planet, we explored range of human cells that can be by this virus. We isolated from patients Toronto, Canada; determined genomic sequences; and identified single-nucleotide changes representative populations our virus stocks. also tested a wide immune for productive infection with SARS-CoV-2. confirm...
Therapeutic monoclonal antibodies that target the conserved stalk domain of influenza virus hemagglutinin and stalk-based universal vaccine strategies are being developed as promising countermeasures for infections. The pan-H1-reactive antibody 6F12 has been extensively characterized shows broad efficacy against divergent H1N1 strains in mouse model. Here we demonstrate its a pandemic challenge ferret model disease. Furthermore, recently strategy based on chimeric constructs focuses immune...
Significance The mechanism of how antiviral antibodies induce Fc–FcγR effector functions remains to be fully elucidated. Although the ability activate is attributed antibody isotype, this does not address why identical isotypes have different capabilities stimulate function. We show that target influenza virus hemagglutinin (HA) require a second intermolecular interaction optimally cells. demonstrate receptor-binding domain HA required bind sialic acid expressed on surface cells optimize...
ABSTRACT Broadly neutralizing antibodies that recognize the conserved hemagglutinin (HA) stalk have emerged as exciting new biotherapeutic tools to combat seasonal and pandemic influenza viruses. Our general understanding of mechanisms by which stalk-specific achieve protection is rapidly evolving. It has recently been demonstrated broadly HA IgG require Fc-Fcγ receptor (FcγR) interactions for optimal in vivo . Here we examine neutrophil effector functions induced antibodies. As most...
As a result of the 2019 novel human coronavirus (COVID-19) global spread, medical examiner/coroner offices will inevitably encounter increased numbers COVID-19-infected decedents at autopsy. While in some cases history fever and/or respiratory distress (eg, cough or shortness breath) may suggest diagnosis, epidemiologic studies indicate that majority individuals infected with COVID-19 develop mild to no symptoms. Those dying with-but not of-COVID-19 still be infectious, however. multiple...
Type I interferons (IFNs) are our first line of defense against virus infection. Recent studies have suggested the ability SARS-CoV-2 proteins to inhibit IFN responses. Emerging data also suggest that timing and extent production is associated with manifestation COVID-19 severity. In spite progress in understanding how activates antiviral responses, mechanistic into wild-type SARS-CoV-2-mediated induction inhibition human type responses scarce. Here we demonstrate infection induces a...
We report on a unique DNA aptamer, denoted MSA52, that displays universally high affinity for the spike proteins of wildtype SARS-CoV-2 as well Alpha, Beta, Gamma, Epsilon, Kappa, Delta and Omicron variants. Using an aptamer pool produced from round 13 selection against S1 domain protein, we carried out one-round SELEX experiments using five different trimeric variants, followed by high-throughput sequencing sequence alignment analysis aptamers formed complexes with all proteins. A...
Abstract High‐precision viral detection at point of need with clinical samples plays a pivotal role in the diagnosis infectious diseases and control global pandemic. However, complexity that often contain very low concentrations makes it huge challenge to develop simple diagnostic devices do not require any sample processing yet are capable meeting performance metrics such as high sensitivity specificity. Herein we describe new single‐pot single‐step electrochemical method uses real‐time...
Although the interleukin-1β converting enzyme (ICE)/CED-3 family of proteases has been implicated recently in neuronal cell death vitro and ovo , role specific genes belonging to this nervous system remains unknown. To address question, we examined vivo expression one these genes, Ice after global forebrain ischemia gerbils. Using RT-PCR Western immunoblot techniques, detected an increase mRNA protein ICE hippocampus during a period 4 d ischemia. Chromatin condensation was observed CA1...
Current influenza virus vaccines rely upon the accurate prediction of circulating strains months in advance actual season order to allow time for vaccine manufacture. Unfortunately, mismatches occur frequently, and even when perfect matches are achieved, suboptimal efficacy leaves several high-risk populations vulnerable infection. However, recent discovery broadly neutralizing antibodies that target hemagglutinin (HA) stalk domain has renewed hope development "universal" may be within...