A5027356771- Hepatitis C virus research
- Hepatitis B Virus Studies
- Monoclonal and Polyclonal Antibodies Research
- SARS-CoV-2 and COVID-19 Research
- Immunotherapy and Immune Responses
- Influenza Virus Research Studies
- COVID-19 Clinical Research Studies
- CAR-T cell therapy research
- SARS-CoV-2 detection and testing
- Systemic Lupus Erythematosus Research
- Animal Virus Infections Studies
- Viral Infections and Immunology Research
- Immunodeficiency and Autoimmune Disorders
- Liver Disease Diagnosis and Treatment
- vaccines and immunoinformatics approaches
- Diabetes and associated disorders
- Endoplasmic Reticulum Stress and Disease
- COVID-19 Impact on Reproduction
- Blood groups and transfusion
- Chronic Lymphocytic Leukemia Research
- Long-Term Effects of COVID-19
- HIV Research and Treatment
- T-cell and B-cell Immunology
- HIV/AIDS drug development and treatment
- Hepatitis Viruses Studies and Epidemiology
Burnet Institute
2012-2024
Memory B cells specific for SARS-CoV-2 spike and nucleocapsid proteins persist in peripheral blood after recovery from COVID-19.
The hepatitis C virus (HCV) glycoproteins E1 and E2 form a heterodimer that mediates CD81 receptor binding viral entry. In this study, we used site-directed mutagenesis to examine the functional role of conserved G436WLAGLFY motif E2. mutants could be placed into two groups based on ability mature virion-incorporated E1E2 bind large extracellular loop (LEL) versus mediate cellular entry pseudotyped retroviral particles. Group 1 comprised where LEL largely correlated with ability,...
A vaccine that prevents hepatitis C virus (HCV) infection is urgently needed to support an emerging global elimination program. However, development has been confounded because of HCV's high degree antigenic variability and the preferential induction type-specific immune responses with limited potency against heterologous viral strains genotypes. We showed previously deletion three variable regions from E2 receptor-binding domain (Δ123) increases ability human broadly neutralizing antibodies...
Abstract The introduction of directly acting antiviral agents (DAAs) has produced significant improvements in the ability to cure chronic hepatitis C infection. However, with over 2% world’s population infected HCV, complications arising from development cirrhosis liver, infection remains leading indication for liver transplantation. Several modelling studies have indicated that DAAs alone will not be sufficient eliminate but if combined an effective vaccine this regimen would provide a...
The E1E2 glycoprotein heterodimer of Hepatitis C virus mediates viral entry. E2 attaches the to cellular receptors; however, function E1 is unknown. We tested hypothesis that a truncated class II fusion protein. mutated amino acids within predicted peptide (residues 276-286) and C-terminal stem-like motif, containing membrane-proximal heptad-repeat sequence 330-347). mutation F285A abolished entry, while other hydrophobic residues had no effect. Alanine replacement blocked entry in three...
Abstract Following the COVID-19 pandemic, novel vaccines have successfully reduced severe disease and death. Despite eliciting lower antibody responses, adenoviral vector are nearly as effective mRNA vaccines. Therefore, protection against may be mediated by immune memory cells. We here evaluated plasma B cells (Bmem) targeting SARS-CoV-2 Spike receptor-binding domain (RBD) elicited vaccine ChAdOx1 (AstraZeneca), their capacity to bind Omicron subvariants, compared this response BNT162b2...
Virus-like particles (VLPs) are highly immunogenic and proven to induce protective immunity. The small surface antigen (HBsAg-S) of hepatitis B virus (HBV) self-assembles into VLPs its use as a vaccine results in antiviral immunity against HBV infections. Chimeric HBsAg-S proteins carrying foreign epitopes allow particle formation have the ability anti-foreign humoral cellular immune responses.The insertion hypervariable region 1 (HVR1) sequence derived from envelope protein 2 (E2) C (HCV)...
ABSTRACT Hepatitis C virus (HCV) envelope glycoproteins E1 and E2 form a heterodimer mediate receptor interactions viral fusion. Both are targets of the neutralizing antibody (NAb) response candidates for production vaccines that generate humoral immunity. Previous studies demonstrated N-terminal hypervariable region 1 (HVR1) can modulate neutralization potential monoclonal antibodies (MAbs), but no information is available on influence HVR2 or intergenotypic variable (igVR) antigenicity. In...
The significant public health problem of Hepatitis C virus (HCV) has been partially addressed with the advent directly acting antiviral agents (DAAs). However, development an effective preventative vaccine would have a impact on HCV incidence and represent major advance towards controlling possibly eradicating globally. We previously reported genotype 1a viral-like particle (VLP) that produced neutralizing antibodies (NAb) T cell responses to HCV. To this approach, we quadrivalent...
In individuals highly exposed to HCV, reinfection is common, suggesting that natural development of sterilising immunity difficult. those are reinfected, some will develop a persistent infection, while small proportion repeatedly clear the virus, protection possible. The aim this study was characterise immune responses associated with rapid clearance HCV reinfection.
Booster vaccinations are recommended to improve protection against severe disease from SARS-CoV-2 infection. With primary involving various adenoviral vector and mRNA-based formulations, it remains unclear if these differentially affect the immune response booster doses. We examined effects of homologous (mRNA/mRNA) heterologous (adenoviral vector/mRNA) vaccination on antibody memory B cell (Bmem) responses ancestral Omicron subvariants. Healthy adults who received BNT162b2 (mRNA) or ChAdOx1...
ABSTRACT The hepatitis C virus glycoprotein E2 receptor-binding domain is encompassed by amino acids 384 to 661 (E2 ) and contains two hypervariable sequences, HVR1 HVR2. sequence comparisons revealed a third variable region, located between residues 570 580, that varies widely genotypes, designated here as igVR, the intergenotypic region. A secreted with simultaneous deletions of three sequences retained its ability bind CD81 conformation-dependent monoclonal antibodies (MAbs) displayed...
The three variable regions of hepatitis C virus (HCV) glycoprotein E2 can be removed simultaneously from the ectodomain (residues 384–661) without affecting folding or CD81 binding. In this study, we show that deletion hypervariable region (HVR) 2 intergenotypic (igVR) in context E1E2 polyprotein eliminates formation heterodimers, reduces binding and abolishes entry. replication competence genomic RNA transcribed JFH1 infectious HCV clone was not affected by HVR1, HVR2 igVR deletions...
The HCV envelope glycoproteins E1 and E2 contain eight 18 highly conserved cysteine residues, respectively. Here, we examined the oxidation state of E1E2 heterodimers incorporated into retroviral pseudotyped particles (HCVpp) investigated significance free sulfhydryl groups in cell culture-derived (HCVcc) HCVpp entry. Alkylation on HCVcc/pp with a membrane-impermeable sulfhydryl-alkylating reagent 4-(N-maleimido)benzyl-α-trimethylammonium iodide (M135) prior to virus attachment cells...
The protonation of histidine in acidic environments underpins its role regulating the function pH-sensitive proteins. For viral fusion proteins, endosome leads to activation their membrane function. HCV (hepatitis C virus) glycoprotein E1-E2 heterodimer mediates within endosome, but roles conserved residues formation a functional and sensing pH changes is unknown. We examined located E1 E2. mutations, H222A/R, H298R H352A, disrupted heterodimerization reduced virus entry. A total five out...
An effective immune response against hepatitis C virus (HCV) requires the early development of multi-specific class 1 CD8+ and II CD4+ T-cells together with broad neutralizing antibody responses. We have produced mammalian-cell-derived HCV virus-like particles (VLPs) incorporating core, E1 E2 genotype 1a to produce such Here we describe biochemical morphological characterization VLPs study core-specific T-cell responses particles. The glycoproteins in formed non-covalent heterodimers core...
•Neutralising antibodies will likely form a key component of an HCV vaccine.•We characterise the immunodominance neutralising and non-neutralising epitopes in primary infection.•We identify that virus genotype might influence targeted.•We also certain epitope target combinations are associated with greater breadth. Background & AimsNeutralising (NAbs) play role clearance HCV. NAbs have been isolated mapped to several domains on envelope proteins. However, these infection remains unknown,...
The E2 glycoprotein of hepatitis C virus (HCV) is the major target broadly neutralizing antibodies (bNAbs) that are critical for efficacy a prophylactic HCV vaccine. We previously showed cell culture–derived, disulfide-linked high-molecular-weight (HMW) form receptor–binding domain lacking three variable regions, Δ123-HMW, elicits broad activity against seven genotypes HCV. A limitation to use this antigen it produced only at low yields and does not have homogeneous composition. Here, we...
Hepatitis C virus glycoprotein E2 contains 18 conserved cysteines predicted to form nine disulfide pairs. In this study, a comprehensive cysteine-alanine mutagenesis scan of all cysteine residues was performed in E1E2-pseudotyped retroviruses (HCVpp) and recombinant receptor-binding domain (E2 384 661 [E2(661)]). All were absolutely required for HCVpp entry competence. The phenotypes individual pairwise mutation disulfides largely the same retrovirion-incorporated E2(661), suggesting their...
The hepatitis C virus (HCV) envelope glycoprotein E2 is the major target of broadly neutralizing antibodies in vivo and focus efforts rational design a universal B cell vaccine against HCV. exhibits high degree amino acid variability which localizes to three discrete regions: hypervariable region 1 (HVR1), 2 (HVR2), intergenotypic variable (igVR). All regions contribute immune evasion and/or isolate-specific structural variations, both important considerations for design. A high-resolution...
The hepatitis C virus (HCV) E2 glycoprotein is a major target of the neutralizing antibody (nAb) response, with multiple type-specific and broadly (bnAb) epitopes identified. 412-to-423 region can generate bnAbs that block interaction cell surface receptor CD81, activity toward HCV genotypes. In this study, we reveal structure rodent monoclonal 24 (MAb24) an extensive contact area peptide spanning region. crystal MAb24-peptide complex reveals paratope bound to hairpin highly similar observed...
ABSTRACT Background Booster vaccinations are recommended to improve protection against severe disease from SARS-CoV-2 infection. With primary involving various adenoviral vector and mRNA-based formulations, it remains unclear if these differentially affect the immune response booster doses. We here examined effects of homologous (mRNA/mRNA) heterologous (adenoviral vector/mRNA) vaccination on antibody memory B cell (Bmem) responses ancestral Omicron subvariants. Methods Healthy adults who...
ABSTRACT Background Lasting immunity to SARS-CoV-2 following infection is questioned because serum antibodies decline in convalescence. However, functional mediated by long-lived memory T and B (Bmem) cells. Objective To determine the longevity immunophenotype of SARS-CoV-2-specific Bmem cells COVID-19 patients. Methods Recombinant spike receptor binding domain (RBD) nucleocapsid protein (NCP) were produced for ELISA-based serology, biotinylated fluorescent tetramer generation identify flow...
We describe a peptide-based strategy for HCV vaccine design that addresses the problem of variability in hypervariable region 1 (HVR1). Peptides representing antibody epitopes HVR1 from genotype 1a were synthesized and incorporated into multideterminant immunogens also included lipid moieties helper T (Th) cell epitopes. Mice inoculated with these polyepitopes generated strong responses. Antibody titers highest mice polyepitope which contained moiety dipalmitoyl-S-glyceryl cysteine...