A5089728223- Influenza Virus Research Studies
- Respiratory viral infections research
- Monoclonal and Polyclonal Antibodies Research
- Immune Response and Inflammation
- Viral gastroenteritis research and epidemiology
- Escherichia coli research studies
- Animal Disease Management and Epidemiology
- vaccines and immunoinformatics approaches
- Receptor Mechanisms and Signaling
- COVID-19 Clinical Research Studies
- Immunotherapy and Immune Responses
- Viral Infections and Outbreaks Research
- Animal Virus Infections Studies
- Virology and Viral Diseases
- Kawasaki Disease and Coronary Complications
- RNA and protein synthesis mechanisms
- Viral Infections and Vectors
- SARS-CoV-2 and COVID-19 Research
- Hepatitis B Virus Studies
- Glycosylation and Glycoproteins Research
- Immune Cell Function and Interaction
- interferon and immune responses
Columbia University
2023
Icahn School of Medicine at Mount Sinai
2014-2019
Columbia University Irving Medical Center
2019
Morgan Stanley Children's Hospital
2019
Massachusetts Institute of Technology
2015
Alternative influenza target There is a pressing need for broadly protective vaccine that can neutralize this constantly varying, deadly virus. Stadlbauer et al. turned their attention away from the current target—the mutable hemagglutinin—and investigated an alternative, less variable virus-coat glycoprotein: neuraminidase. The authors extracted monoclonal antibodies (mAbs) human donor naturally infected with H3N2 virus subtype. In mice, mAbs were against A groups 1 and 2 (human, avian,...
ABSTRACT In an attempt to assess the cross-protective potential of influenza virus neuraminidase (NA) as a vaccine antigen, different subtypes recombinant NA were expressed in baculovirus system and used vaccinate mice prior lethal challenge with homologous, heterologous, or heterosubtypic viruses. Mice immunized subtype N2 completely protected from morbidity mortality homologous displayed significantly reduced viral lung titers. Heterologous drifted strain resulted but no mortality. Similar...
Influenza virus infections are a major public health concern and cause significant morbidity mortality worldwide. Current vaccines effective but strain specific due to their focus on the immunodominant globular head domain of hemagglutinin (HA). It has been hypothesized that sequential exposure humans hemagglutinins with divergent domains conserved stalk could refocus immune response broadly neutralizing epitopes in stalk. Humans have preexisting immunity against H1 (group 1 hemagglutinin),...
Influenza viruses evade human adaptive immune responses due to continuing antigenic changes. This makes it necessary re-formulate and re-administer current seasonal influenza vaccines on an annual basis. Our pan-influenza vaccination approach attempts redirect antibody from the variable, immuno-dominant hemagglutinin head towards conserved-but immuno-subdominant-hemagglutinin stalk. The strategy utilizes sequential immunization with chimeric hemagglutinin-based expressing exotic domains, a...
BackgroundInfluenza viruses cause substantial annual morbidity and mortality globally. Current vaccines protect against influenza only when well matched to the circulating strains. However, antigenic drift can considerable mismatches between vaccine strains, substantially reducing effectiveness. Moreover, current seasonal are ineffective pandemic influenza, production of a newly emerging virus strain takes months. Therefore, there is an unmet medical need for broadly protective vaccine. We...
Protection from influenza virus infection is canonically associated with antibodies that neutralize the by blocking interaction between viral hemagglutinin and host cell receptors. However, protection can also be conferred other mechanisms, including antibody-mediated effector functions. Here, we report characterization of 22 broadly cross-reactive, nonneutralizing specific for B hemagglutinin. The majority these recognized viruses isolated over period 73 years bind conserved stalk domain A...
ABSTRACT Between November 2013 and February 2014, China reported three human cases of H10N8 influenza virus infection in the Jiangxi province, two which were fatal. Using hybridoma technology, we isolated a panel H10- N8-directed monoclonal antibodies (MAbs) further characterized binding reactivity these (via enzyme-linked immunosorbent assay) to range purified recombinant protein substrates. The H10-directed MAbs displayed functional hemagglutination inhibition (HI) neutralization activity,...
SARS-CoV-2 infection for most children results in mild or minimal symptoms, though rare cases severe disease can develop, including a multisystem inflammatory syndrome (MIS-C) with myocarditis. Here, we present longitudinal profiling of immune responses during acute and following recovery who developed MIS-C, relative to experienced more typical symptoms COVID-19. T cells MIS-C exhibited transient signatures activation, inflammation, tissue residency which correlated cardiac severity, while...
Ad4-H5 vaccine induces prolonged increases in H5-specific B cell frequency, antibody affinity, and somatic hypermutation.
ABSTRACT Influenza viruses expressing chimeric hemagglutinins (HAs) are important tools in the quest for a universal vaccine. Using cryo-electron tomography, we have determined structures of HA variant that comprises an H1 stalk and H5 globular head domain (cH5/1 HA) native antibody-bound states. We show cH5/1 is structurally different from HA, displaying 60° rotation between groups, leading to novel unexpected “open” arrangement trimers. cH5/1N1 also display higher glycoprotein density than...
Out of an estimated 31,100 cases since their discovery in 1976, ebolaviruses have caused approximately 13,000 deaths. The vast majority (∼11,000) these occurred during the 2013-2016 West African epidemic. Three out five species genus are known to cause Ebola Virus Disease humans. Several monoclonal antibodies against ebolavirus glycoprotein currently development as therapeutics. However, there is still a paucity that can cross-react between glycoproteins different species, and mechanism...
The standard method to quantify the hemagglutinin content of influenza virus vaccines is single radial immunodiffusion assay. This assay primarily relies on polyclonal antibodies against head domain hemagglutinin, which main target antigen vaccines. Novel vaccine candidates that redirect immune response towards evolutionary more conserved stalk, including chimeric and headless constructs, are highly dependent structural integrity protein present conformational epitopes for neutralizing...
Significant genetic variability in the head region of influenza A hemagglutinin, main target current vaccines, makes it challenging to develop a long-lived seasonal prophylaxis. Vaccines based on conserved hemagglutinin stalk domain might provide broader cross-reactive immunity. However, this is immunosubdominant region. Peptide-based vaccines have gained much interest as they allow immune system focus relevant but less immunogenic epitopes. We developed novel hemagglutinin-based display...
Three cases of influenza A(H10N8) virus infection in humans have been reported; 2 these infected persons died. Characterization the receptor binding pattern H10 hemagglutinin from avian and human isolates showed that both interact weakly with human-like receptors maintain strong affinity for avian-like receptors.
Influenza viruses exhibit a remarkable ability to adapt and evade the host immune response. One way is through antigenic changes that occur on surface glycoproteins of virus. The generation escape variants powerful method in elucidating how detection identifying critical residues required for antibody binding. Here, we describe protocol generate influenza A virus by utilizing human or murine monoclonal antibodies (mAbs) directed against viral hemagglutinin (HA). With use our technique,...
Influenza viruses exhibit a remarkable ability to adapt and evade the host immune response. One way is through antigenic changes that occur on surface glycoproteins of virus. The generation escape variants powerful method in elucidating how detection identifying critical residues required for antibody binding. Here, we describe protocol generate influenza A virus by utilizing human or murine monoclonal antibodies (mAbs) directed against viral hemagglutinin (HA). With use our technique,...