A5085016318- Immunotherapy and Immune Responses
- SARS-CoV-2 and COVID-19 Research
- COVID-19 Clinical Research Studies
- T-cell and B-cell Immunology
- vaccines and immunoinformatics approaches
- Immune Cell Function and Interaction
- Viral Infections and Outbreaks Research
- HIV Research and Treatment
- CAR-T cell therapy research
- Virology and Viral Diseases
- Immunodeficiency and Autoimmune Disorders
- Viral Infections and Vectors
- HIV/AIDS Research and Interventions
- Virus-based gene therapy research
- Immune responses and vaccinations
- Mosquito-borne diseases and control
Ragon Institute of MGH, MIT and Harvard
2020-2025
Massachusetts General Hospital
2023
Harvard University
2020-2021
Tufts University
2020
The SARS-CoV-2 Omicron variant (B.1.1.529) contains mutations that mediate escape from antibody responses, although the extent to which these substitutions in spike and non-spike proteins affect T cell recognition is unknown. In this study, we show responses individuals with prior infection, vaccination, both infection boosted vaccination are largely preserved proteins. However, also identify a subset of (∼21%) >50% reduction reactivity spike. Evaluation functional CD4
The Ebola virus (EBOV) envelope glycoprotein (GP) is a membrane fusion machine required for entry into cells. Following endocytosis of EBOV, the GP1 domain cleaved by cellular cathepsins in acidic endosomes, removing glycan cap and exposing binding site Niemann-Pick C1 (NPC1) receptor. NPC1 to entry. How this interaction translates GP2 domain-mediated viral endosomal membranes not known. Here, using bulk fluorescence dequenching assay single-molecule Förster resonance energy transfer...
Individuals with primary and pharmacologic B cell deficiencies have high rates of severe disease mortality from coronavirus 2019 (COVID-19), but the immune responses clinical outcomes after acute respiratory syndrome 2 (SARS-CoV-2) infection vaccination yet to be fully defined. Here, we evaluate cellular both SARS-CoV-2 in patients receiving anti-CD20 therapy rituximab (RTX) those low counts due common variable deficiency (CVID) disease. Assessment effector memory CD4 + CD8 T revealed...
The SARS-CoV-2 Omicron variant (B.1.1.529) contains mutations that mediate escape from infection and vaccine-induced antibody responses, although the extent to which these substitutions in spike non-spike proteins affect T cell recognition is unknown. Here we show responses individuals with prior infection, vaccination, both boosted vaccination are largely preserved proteins. However, also identify a subset of (∼21%) >50% reduction reactivity spike. Evaluation functional CD4 + CD8 memory...
Defining factors that govern CD8+ T cell immunodominance is critical for the rational design of vaccines viral pathogens. Here, we assess contribution human leukocyte antigen (HLA) class-I-peptide stability 186 optimal HIV epitopes across 18 HLA alleles using transporter associated with processing (TAP)-deficient mono-allelic HLA-expressing lines. We find immunodominant increase surface stabilization class-I molecules in comparison to subdominant epitopes. also strongly correlated overall...
Memory lymphocytes are durable cells that persist in the absence of antigen, but few human B cell subsets have been characterized terms durability. The relative durability eight non-overlapping sub-populations covering 100% all class-switched was interrogated. Only two long-lived populations persisted antigen. In addition to canonical germinal center-derived switched-memory with an IgD-CD27+CXCR5+ phenotype, a second, non-canonical, distinct memory population IgD-CD27-CXCR5+ DN1 also...
The Ebola virus (EBOV) envelope glycoprotein (GP) mediates the fusion of virion membrane with susceptible target cells during infection. While proteolytic cleavage GP by endosomal cathepsins and binding cellular receptor Niemann-Pick C1 protein (NPC1) are essential steps for entry, detailed mechanisms which these events promote remain unknown. Here, we applied single-molecule Förster resonance energy transfer (smFRET) imaging to investigate structural dynamics EBOV trimeric ectodomain,...
Abstract In previously unvaccinated and uninfected individuals, non-RBD SARS-CoV-2 spike-specific B cells were prominent in two distinct, durable, resting, cross-reactive, “pre-existing” switched memory cell compartments. While pre-existing RBD-specific extremely rare these compartments molded by vaccination infection to become the primary source of that are triggered vaccine boosting. The frequency wild-type RBD-binding cross-react with Omicron variant RBD did not alter contrast, after a...
Memory lymphocytes are durable cells that persist in the absence of antigen, but few human B cell subsets have been characterized terms durability. The relative durability eight non-overlapping sub-populations covering 100% all class-switched was interrogated. Only two long-lived populations persisted antigen. In addition to canonical germinal center-derived switched-memory with an IgD-CD27+ CXCR5+ phenotype, a second, non-canonical, distinct memory population IgD-CD27- DN1 also durable,...