A5003875832- SARS-CoV-2 and COVID-19 Research
- COVID-19 Clinical Research Studies
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- T-cell and B-cell Immunology
- Influenza Virus Research Studies
- Monoclonal and Polyclonal Antibodies Research
- Animal Virus Infections Studies
- COVID-19 epidemiological studies
- vaccines and immunoinformatics approaches
- Respiratory viral infections research
- Bacillus and Francisella bacterial research
- SARS-CoV-2 detection and testing
- HIV Research and Treatment
- Viral gastroenteritis research and epidemiology
- Viral Infections and Immunology Research
- Long-Term Effects of COVID-19
- Lymphadenopathy Diagnosis and Analysis
- Blood groups and transfusion
- Inflammasome and immune disorders
- IL-33, ST2, and ILC Pathways
- Immune Response and Inflammation
- Neuroendocrine Tumor Research Advances
- Cell Adhesion Molecules Research
- Complement system in diseases
Peter Doherty Institute
2017-2025
The University of Melbourne
2017-2025
Australian Research Council
2020-2021
Monash University
2021
The durability of infection-induced SARS-CoV-2 immunity has major implications for reinfection and vaccine development. Here, we show a comprehensive profile antibody, B cell T dynamics over time in cohort patients who have recovered from mild-moderate COVID-19. Binding neutralising antibody responses, together with individual serum clonotypes, decay the first 4 months post-infection. A similar decline Spike-specific CD4+ circulating follicular helper frequencies occurs. By contrast,...
Abstract The hallmarks of COVID-19 are higher pathogenicity and mortality in the elderly compared to children. Examining baseline SARS-CoV-2 cross-reactive immunological responses, induced by circulating human coronaviruses (hCoVs), is needed understand such divergent clinical outcomes. Here we show analysis coronavirus antibody responses pre-pandemic healthy children ( n = 89), adults 98), 57), patients 50) systems serology. Moderate levels cross-reactive, but non-neutralizing, antibodies...
Protein-based, self-assembling nanoparticles elicit superior immunity compared with soluble protein vaccines, but the immune mechanisms underpinning this effect remain poorly defined. Here, we investigated immunogenicity of a prototypic ferritin-based nanoparticle displaying influenza hemagglutinin (HA) in mice and macaques. Vaccination HA-ferritin elicited higher serum antibody titers greater protection against experimental challenge HA protein. Germinal centers draining lymph nodes were...
Influenza B viruses (IBV) drive a significant proportion of influenza-related hospitalisations yet are understudied compared to influenza A. Current vaccines target the head viral hemagglutinin (HA) which undergoes rapid mutation, significantly reducing vaccine effectiveness. Improved control IBV needed. Here we developed novel HA probes interrogate humoral responses in humans. A HA-specific cells recognise both B/Victoria/2/87-like and B/Yamagata/16/88-like lineages distinct pattern...
Abstract SARS-CoV-2 vaccines are advancing into human clinical trials, with emphasis on eliciting high titres of neutralising antibodies against the viral spike (S). However, merits broadly targeting S versus focusing antibody onto smaller receptor binding domain (RBD) unclear. Here we assess prototypic and RBD subunit in homologous or heterologous prime-boost regimens mice non-human primates. We find is highly immunogenic mice, while comparatively poor immunogenicity associated limiting...
Recent studies have established that memory B cells, largely thought to be circulatory in the blood, can take up long-term residency inflamed tissues, analogous widely described tissue-resident T cells. The dynamics of recruitment and retention cells tissues their immunological purpose remains unclear. Here, we characterized (B RM ) are stably maintained lungs mice after pulmonary influenza infection. Influenza - specific were localized within inducible bronchus-associated lymphoid (iBALTs)...
Both natural influenza infection and current seasonal vaccines primarily induce neutralizing antibody responses against highly diverse epitopes within the “head” of viral hemagglutinin (HA) protein. There is increasing interest in redirecting immunity toward more conserved HA stem or stalk as a means broadening protective responses. Here we examined stem–specific B cell T follicular helper (Tfh) context immunization mouse monkey models. We found that during infection, domain was...
Abstract Mucosal-associated invariant T (MAIT) cells produce inflammatory cytokines and cytotoxic granzymes in response to by-products of microbial riboflavin synthesis. Although MAIT are protective against some pathogens, we reasoned that they might contribute pathology chronic bacterial infection. We observed proximity Helicobacter pylori bacteria human gastric tissue, so, using MR1-tetramers, examined whether gastritis a mouse H. SS1 infection model. Following infection, accumulated high...
Potent neutralizing monoclonal antibodies are one of the few agents currently available to treat COVID-19. SARS-CoV-2 variants concern (VOCs) that carry multiple mutations in viral spike protein can exhibit neutralization resistance, potentially affecting effectiveness some antibody-based therapeutics. Here, generation a diverse panel 91 human, provides an in-depth structural and phenotypic definition receptor binding domain (RBD) antigenic sites on spike. These RBD ameliorate infection mice...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) breakthrough infection of vaccinated individuals is increasingly common with the circulation highly immune evasive and transmissible Omicron variants. Here, we report dynamics durability recalled spike-specific humoral immunity following BA.1 or BA.2 infection, longitudinal sampling up to 8 months after infection. Both infections robustly boosted neutralization activity against infecting strain while expanding breadth BA.4,...
Seasonally recurrent influenza virus infections are a significant cause of global morbidity and mortality. In murine models, primary infection in the respiratory tract elicits potent humoral responses concentrated draining mediastinal lymph node spleen. addition to immunity within secondary lymphoid organs (SLO), pulmonary is also associated with formation ectopic inducible bronchus-associated tissues (iBALT) lung. These structures display organisation, but their function protective benefits...
Despite remarkable successes of immunization in protecting public health, safe and effective vaccines against a number life-threatening pathogens such as HIV, ebola, influenza, SARS-CoV-2 remain urgently needed. Subunit can avoid potential toxicity associated with traditional whole virion-inactivated live-attenuated vaccines; however, the immunogenicity subunit is often poor. A facile method here reported to produce lipid nanoparticle that exhibit high elicit protection influenza virus....
Repeated mRNA COVID-19 vaccination increases spike-specific immunoglobulin G4 (IgG4) titers. Here, we characterized the influence of increased IgG4 titers on a range Fc-mediated responses. Elevated reduced binding to FcγRIIIa and decreased antibody-dependent cellular cytotoxicity. However, in individuals with lower total IgG, acted synergy other IgG subclasses improve FcγRI FcγRIIa consequently phagocytosis. Furthermore, this trend was more pronounced recent SARS-CoV-2 variants where induced...
Abstract Human clinical trials have reported immunological outcomes can differ between ipsilateral (same side) and contralateral (alternate sides) prime-boost vaccination. However, our mechanistic understanding of how keeping or shifting the anatomical sites immunization impacts resultant germinal centers (GCs) antibody responses is limited. Here, we use an adjuvanted SARS-CoV-2 spike vaccine to dissect GC dynamics in draining lymph nodes serological following vaccination C57BL/6 mice....
Abstract SARS-CoV-2, the pandemic coronavirus that causes COVID-19, has infected millions worldwide, causing unparalleled social and economic disruptions. COVID-19 results in higher pathogenicity mortality elderly compared to children. Examining baseline SARS-CoV-2 cross-reactive immunological responses, induced by circulating human coronaviruses, is critical understand such divergent clinical outcomes. The cross-reactivity of antibody responses healthy children (n=89), adults (n=98),...
Endemic human coronaviruses (hCoVs) circulate worldwide but cause minimal mortality. Although seroconversion to hCoV is near ubiquitous during childhood, little known about hCoV-specific T-cell memory in adults.We quantified CD4 and antibody responses spike antigens 42 SARS-CoV-2-uninfected individuals. Antigen-specific T cells circulating follicular helper (cTFH) were identified using an activation-induced marker assay characterised for phenotype chemokine receptor expression.T-cell...
Abstract Objectives Amino acid variations across more than 30 immunoglobulin (Ig) allotypes may introduce structural changes that influence recognition by anti‐Ig detection reagents, consequently confounding interpretation of antibody responses, particularly in genetically diverse cohorts. Here, we assessed a panel commercial monoclonal anti‐IgG1 clones for capacity to universally recognise two dominant IgG1 haplotypes (G1m‐1,3 and G1m1,17). Methods Four anti‐human were via ELISAs multiplex...
BACKGROUNDThere is uncertainty about the timing of booster vaccination against COVID-19 in highly vaccinated populations during present endemic phase COVID-19. Studies focused on primary have previously suggested improved immunity with a longer interval between first and second vaccine doses.METHODSWe conducted randomized, controlled trial (November 2022-August 2023) assigned 52 fully adults to an immediate or 3-month delayed bivalent Spikevax mRNA vaccine. Follow-up visits were completed...
The rapid global spread of SARS-CoV-2 and resultant mortality social disruption have highlighted the need to better understand coronavirus immunity expedite vaccine development efforts. Multiple candidate vaccines, designed elicit protective neutralising antibodies targeting viral spike glycoprotein, are rapidly advancing clinical trial. However, immunogenic properties protein in humans unresolved. To address this, we undertook an in-depth characterisation humoral cellular against following...
The durability of infection-induced SARS-CoV-2 immunity has major implications for public health mitigation and vaccine development. Animal studies 1,2 the scarcity confirmed re-infection 3 suggests immune protection is likely, although this debated. Lasting following acute viral infection requires maintenance both serum antibody antigen-specific memory B T lymphocytes notoriously pathogen specific, ranging from life-long smallpox or measles 4 , to highly transient common cold coronaviruses...
Abstract Humans are exposed to influenza virus through periodic infections. Due these repeated exposures, human populations commonly have elevated antibody titers targeting the conserved internal nucleoprotein (NP). Despite presence of anti‐NP antibodies, humans acutely susceptible drifted viruses with antigenically different surface proteins and protective potential NP antibodies is unclear. In this study, high levels NP‐specific B cells were detected in both adult influenza‐infected mice,...