A5062939266- SARS-CoV-2 and COVID-19 Research
- Influenza Virus Research Studies
- Monoclonal and Polyclonal Antibodies Research
- Complement system in diseases
- Immunotherapy and Immune Responses
- COVID-19 Clinical Research Studies
- Viral gastroenteritis research and epidemiology
- Respiratory viral infections research
- Animal Virus Infections Studies
- Immune Cell Function and Interaction
- vaccines and immunoinformatics approaches
- T-cell and B-cell Immunology
- Cell Adhesion Molecules Research
- SARS-CoV-2 detection and testing
- Erythrocyte Function and Pathophysiology
- Platelet Disorders and Treatments
- Virus-based gene therapy research
- Diabetes and associated disorders
- Virology and Viral Diseases
- Diet, Metabolism, and Disease
- Pancreatic function and diabetes
- Phagocytosis and Immune Regulation
- Bacteriophages and microbial interactions
- Chronic Lymphocytic Leukemia Research
- CRISPR and Genetic Engineering
Icahn School of Medicine at Mount Sinai
2021-2025
Harvard University
2016-2022
Boston Children's Hospital
2016-2021
Ragon Institute of MGH, MIT and Harvard
2021
New York Proton Center
2021
Mount Sinai Health System
2021
Aarhus University
2012-2016
Université de Montpellier
2016
Laboratory of Pathogens and Host Immunity
2016
Lundbeck Foundation
2016
Significance Antigenic variation requires frequent revision of annual influenza vaccines. Next-generation vaccine design strategies aim to elicit a broader immunity by directing the human immune response toward conserved sites on principal viral surface protein, hemagglutinin (HA). We describe group antibodies that recognize hitherto unappreciated, site HA H1 subtype viruses. Mutations in site, which required change component 2017 vaccine, had not previously “taken over” among circulating...
Significance Fragments of complement component C3 tag surfaces such as those presented by microbial pathogens or dying host cells for recognition from the innate immune system. Complement receptor (CR) 3 enables efficient binding complement-tagged macrophages and dendritic cells, which eventually transport CR3-bound material into lymph nodes. The study identifies in atomic details fragments CR3 required binding. structural organization permits concomitant another receptor, namely CR2,...
Understanding the naïve B cell repertoire and its specificity for potential zoonotic threats, such as highly pathogenic avian influenza (HPAI) H5Nx viruses, may allow prediction of infection- or vaccine-specific responses. However, this possibility to respond emerging, prepandemic viruses are largely undetermined. Here, we profiled reactivity against a prototypical HPAI H5 hemagglutinin (HA), major target antibody We found that frequency H5-specific human cells targeting HA “head” domain was...
SUMMARY Public antibodies that recognize conserved epitopes are critical for vaccine development, and identifying somatic hypermutations (SHMs) enhance antigen affinity in these public responses is key to guiding design better protection. We propose affinity-enhancing SHMs selectively enriched antibody clonotypes, surpassing the background frequency seen carrying same V genes, but with different epitope specificities. Employing a human IGHV4-59 / IGKV3-20 as model, we compare SHM signatures...
Epitope-focused approaches for selective clonal induction of broadly neutralizing antibodies (bnAbs) inform most current vaccine strategies influenza virus and other rapidly evolving pathogens. The two conserved epitopes on the hemagglutinin (HA) - "stem" receptor-binding site (RBS) "head" are focus "universal" development efforts. Because stem-directed serum bnAbs much less abundant than head-directed ones, we hypothesized that HA stem may be autoreactive thus eliminated through mechanisms...
Initial exposure to a pathogen elicits an adaptive immune response control and eradicate the threat. Interrogating abundance specificity of naive B cell repertoire drives understanding how mount protective responses. Here, we isolated cells from eight seronegative human donors targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor binding domain (RBD). Single-cell (BCR) sequencing identified diverse gene usage no restriction on complementarity determining region...
Immunization or microbial infection can establish long-term B cell memory not only systemically but also locally. Evidence has suggested that local contributes to early plasmacytic responses after secondary challenge. However, it is unclear whether locality of immunization plays any role in participation recall germinal centers (GCs), which essential for updating their antigen receptors (BCRs). Using single culture and fate mapping, we have characterized BCR repertoires GCs boost...
Neutralizing antibodies correlate with protection against SARS-CoV-2. Recent studies, however, show that binding antibody titers, in the absence of robust neutralizing activity, also from disease progression. Non-neutralizing cannot directly protect infection but may recruit effector cells thus contribute to clearance infected cells. Also, they often bind conserved epitopes across multiple variants. We characterized 42 human mAbs COVID-19 vaccinated individuals. Most these exhibited no activity
Complement is a part of innate immunity that has critical role in the protection against microbial infections, bridges with adaptive and initiates inflammation. Activation complement, by specific recognition molecular patterns presented an activator, for example, pathogen cell, classical lectin pathways or spontaneously alternative pathway, leads to opsonization activator production pro-inflammatory molecules such as C3a anaphylatoxin. The biological function this anaphylatoxin regulated...
Summary In this study we profiled vaccine-induced polyclonal antibodies as well plasmablast derived mAbs from individuals who received SARS-CoV-2 spike mRNA vaccine. Polyclonal antibody responses in vaccinees were robust and comparable to or exceeded those seen after natural infection. However, the ratio of binding neutralizing vaccination was greater than that infection and, at monoclonal level, found majority did not have activity. We also a co-dominance targeting NTD RBD an original...
Despite the availability of licensed vaccines, influenza causes considerable morbidity and mortality worldwide. Current vaccines elicit an immune response that primarily targets head domain viral glycoprotein hemagglutinin (HA). Influenza viruses, however, readily evade this by acquiring mutations in domain. While target more conserved HA stalk may circumvent problem, low levels antistalk antibodies are elicited vaccination, possibly due to poor accessibility B cell receptors. In work, it is...
Therapeutic monoclonal antibodies (mAbs) have been studied in humans, but the impact on immune memory of mAb treatment during an ongoing infection remains unclear. We evaluated effect infusion anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike receptor-binding domain (RBD) bamlanivimab B cells (MBCs) SARS-CoV-2-infected individuals. Bamlanivimab skewed repertoire MBCs targeting toward non-RBD epitopes. Furthermore, relative affinity RBD was weaker mAb-treated individuals...
Follicular dendritic cells (FDCs), a rare and enigmatic stromal cell type in the B follicles of secondary lymphoid organs, store present antigen to cells. While essential for germinal center (GC) responses, their exact role during GC selection remains unknown. FDCs upregulate inhibitory IgG Fc receptor FcγRIIB formation. We show that deficiency does not affect frequencies compared wild-type mice. However, absence on FDCs, GCs aberrant autoreactive selective foreign responses. These are more...