A5028896091- Influenza Virus Research Studies
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- vaccines and immunoinformatics approaches
- SARS-CoV-2 and COVID-19 Research
- Animal Disease Management and Epidemiology
- COVID-19 Clinical Research Studies
- COVID-19 epidemiological studies
- interferon and immune responses
- Immune Response and Inflammation
- Numerical Methods and Algorithms
- Diabetes and associated disorders
- Tryptophan and brain disorders
- Matrix Theory and Algorithms
- Blood groups and transfusion
- Cell Adhesion Molecules Research
- Viral Infections and Vectors
- Monoclonal and Polyclonal Antibodies Research
- Respiratory viral infections research
University of Rochester Medical Center
2010-2022
University of Rochester
2005-2020
National Jewish Health
2009
University of Colorado Denver
2009
The recent rapid worldwide spread of SARS-CoV-2 has established a pandemic potentially serious disease in the highly susceptible human population. Key issues are whether humans have preexisting immune memory that provides some protection against and infection generates lasting reinfection. Our analysis focused on pre- postinfection IgG B cells (MBCs) reactive to proteins. Most importantly, we demonstrate both MBCs novel receptor binding domain conserved S2 subunit spike protein. Thus, even...
Tissue-resident memory CD8 T (T RM ) cells are a unique immune subset that develops and remains in peripheral tissues at the site of infection, providing future host resistance upon reexposure to pathogen. In pulmonary system, identified through S1P antagonist CD69 expression integrins CD103/β7 CD49a/CD29(β1). Contrary established role on cells, functions CD103 CD49a this population not well defined. This study examines patterns with specific focus their impact cell motility during influenza...
Memory B cells (MBCs) are key determinants of the cell response to influenza virus infection and vaccination, but effect different forms antigen exposure on MBC populations has received little attention. We analyzed peripheral blood mononuclear plasma collected following human H3N2 investigate relationship between hemagglutinin-specific antibody production changes in size character hemagglutinin-reactive populations. Infection produced increased concentrations IgG reactive H3 head infecting...
The unexpected emergence of pandemic H1N1 influenza has generated significant interest in understanding immunological memory to and how previous encounters with seasonal strains influence our ability respond novel strains. In this study, we evaluate the T cell repertoire healthy adults determine abundance protein specificity influenza-reactive CD4 cells, using an unbiased empirical approach, assess cells recognize epitopes naturally by infection virus. Our studies revealed that most...
Abstract The ability to track CD4 T cells elicited in response pathogen infection or vaccination is critical because of the role these play protective immunity. Coupled with advances genome sequencing pathogenic organisms, there considerable appeal for implementation computer-based algorithms predict peptides that bind class II molecules, forming complex recognized by cells. Despite recent progress this area, a paucity data regarding success identifying actual pathogen-derived epitopes. In...
The induction of antibodies specific for the influenza HA protein stalk domain is being pursued as a universal strategy against virus infections. However, little work has been done looking at natural or induced antigenic variability in this and effects on viral fitness. We analyzed human H1 head sequences found substantial both, although was highest region. Furthermore, using immune sera from pandemic A/California/04/2009 subjects mAbs domain, viruses were selected vitro containing mutations...
The specificity of the CD4 T-cell immune response to influenza virus is influenced by genetic complexity and periodic encounters with variant subtypes strains. In order understand what controls reactivity proteins how virus-specific memory compartment shaped over time, it first necessary diversity primary response. study reported here, we have used an unbiased approach evaluate peptide T cells elicited after live infection. We focused on four viral that distinct intracellular distributions...
ABSTRACT The recent threat of an avian influenza pandemic has generated significant interest in enhancing our understanding the events that dictate protective immunity to and generating vaccines can induce heterosubtypic immunity. Although antigen-specific CD4 T cells are known play a key role through provision help B CD8 cells, little is about specificity diversity elicited after infection, particularly those humans. In this study, we used HLA-DR transgenic mice directly comprehensively...
DM edits the peptide repertoire presented by major histocompatibility complex class II molecules professional antigen-presenting cells (APCs), favoring presentation of some peptides over others. Despite considerable research many laboratories, there is still significant uncertainty regarding biochemical attributes II–peptide complexes that govern their susceptibility to editing. Here, using APCs either do or not express and a set unrelated antigens, we found intrinsic kinetic stability...
Influenza is a contagious, acute respiratory disease that major cause of morbidity and mortality throughout the world. CD4 T cells play an important role in immune response to this pathogen through secretion antiviral cytokines, by providing help CD8 B promote development immunological memory neutralizing antibody responses. Despite these well-defined roles anti-influenza response, our understanding T-cell diversity specificity remains limited. In study reported here, overlapping peptides...
The emergence of avian H7N9 viruses has raised concerns about its pandemic potential and prompted vaccine trials. At present, it is unknown whether there will be sufficient cross-reactive hemagglutinin (HA)–specific CD4 T-cell memory with seasonal influenza to facilitate antibody production H7 HA. There also been speculation that have few epitopes. In this study, we quantified the provide T cells can cross-reactively recognize HA–derived peptides. These studies revealed many humans...
Abstract Nanoparticle vaccines based on H. pylori ferritin are increasingly used as a vaccine platform for many pathogens, including RSV, influenza, and SARS-CoV-2. They have been found to elicit enhanced, long-lived B cell responses. The basis improved efficacy of nanoparticle remains unresolved, whether recruitment CD4 T cells specific the component these contributes cognate help in response. Using influenza HA-ferritin nanoparticles prototype, we performed an unbiased assessment epitope...
Abstract Immunodominance refers to the restricted peptide specificity of T cells that are detectable after an adaptive immune response. For CD4 cells, many mechanisms used explain this selectivity suggest events related Ag processing play a major role in determining peptide’s ability recruit cells. Implicit these models is prediction molecular context which antigenic contained will impact significantly on its immunodominance. In study, we present evidence cell responses peptides within...
Abstract Currently, licensed influenza virus vaccines are designed and tested only for their ability to elicit hemagglutinin (HA)-reactive, neutralizing antibodies. Despite this, the purification process in vaccine manufacturing often does not completely remove other virion components. In studies reported here, we have examined viral protein composition of a panel from different manufacturers years. Using western blotting, found that, beyond HA proteins, there detectable quantities...
Abstract The most effective measure to induce protection from influenza is vaccination. Thus, yearly vaccination recommended, which, together with infections, establishes diverse repertoires of B cells, antibodies, and T cells. We examined the impact this accumulated immunity on human responses in adults split, subunit, recombinant protein-based vaccines. Enzyme-linked immunosorbent assay (ELISA) assays, quantify serum peptide-stimulated CD4 T-cell cytokine ELISpots revealed that preexisting...
A major gap in our understanding of the immune response to pathogens and vaccines is how closely antigen specificity memory phase mimics repertoire that rapidly expanded upon priming. Understanding diversity CD4 T-cell compartment after a primary hampered by technical challenges epitope discovery suitable models study responses. Recently, we have used overlapping synthetic peptides empirically map most specificities present live influenza infection. We found can be exceptionally diverse,...
ABSTRACT The high susceptibility of humans to SARS-CoV-2 infection, the cause COVID-19, reflects novelty virus and limited preexisting B cell immunity. IgG against spike (S) protein, which carries novel receptor binding domain (RBD), is absent or at low levels in unexposed individuals. To better understand response we asked whether virus-reactive memory cells (MBCs) were present subjects MBC generation accompanied virus-specific production infected subjects. We analyzed sera PBMCs from...
Avian influenza vaccines exhibit poor immunogenicity in humans. We hypothesized that one factor underlying weak B cell responses was sequence divergence between avian and seasonal hemagglutinin proteins, thus limiting the availability of adequate CD4 T help. To test this, a novel chimeric protein (cH7/3) derived, comprised stem domain from H3 head H7. Immunological memory to established mice, through strategies included inactivated vaccines, Flumist, synthetic peptides derived stalk domain....
Immunodominance refers to the highly selective peptide reactivity of T cells during an immune response. In this study, we tested hypothesis that persistence peptide:class II complexes is one key parameter selects final specificity CD4 cells. We found low-stability support initial priming and expansion cells, but becomes strikingly aborted in presence competitive cell responses unrelated peptides. Our experiments revealed for inhibition occur, must be initiated by same antigen presenting...
The ability of peptides to form stable complexes with MHC class II molecules expressed in the host determines their recruit CD4 T cells during an immune response. In this study, we sought define features antigenic that control kinetic stability I-A(d) because diversity molecule is known present. Peptide dissociation assays indicated each pocket displays exquisite sensitivity side chain structure, size, and charge. Most surprising were results related P1 pocket, which has been difficult by...