A5003699560- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- HIV Research and Treatment
- Immunotherapy and Immune Responses
- Monoclonal and Polyclonal Antibodies Research
- SARS-CoV-2 and COVID-19 Research
- HIV/AIDS drug development and treatment
- DNA Repair Mechanisms
- COVID-19 Clinical Research Studies
- CRISPR and Genetic Engineering
- Glycosylation and Glycoproteins Research
- vaccines and immunoinformatics approaches
- Cytomegalovirus and herpesvirus research
- HIV/AIDS Research and Interventions
- Immunodeficiency and Autoimmune Disorders
- CAR-T cell therapy research
- SARS-CoV-2 detection and testing
- Animal Virus Infections Studies
- Immune Response and Inflammation
- Genomics and Chromatin Dynamics
- Mosquito-borne diseases and control
- Carcinogens and Genotoxicity Assessment
- Viral gastroenteritis research and epidemiology
- Long-Term Effects of COVID-19
- Transgenic Plants and Applications
Rockefeller University
2016-2025
Howard Hughes Medical Institute
2016-2025
Yale University
2021
Center for Molecular Medicine and Immunology
2012-2021
University of Massachusetts Chan Medical School
2021
New York Proton Center
2019
Boston Children's Hospital
2018
Massachusetts General Hospital
2016
Universidade de São Paulo
2014
Center of Molecular Immunology (Cuba)
2001-2014
Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 987 patients with life-threatening disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-ω (IFN-ω) (13 patients), 13 types IFN-α (36), or both (52) onset critical disease; a few also auto-Abs other three type I IFNs. The neutralize ability corresponding IFNs to block...
During the coronavirus disease-2019 (COVID-19) pandemic, severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) has led to infection of millions people and claimed hundreds thousands lives. The entry virus into cells depends on receptor-binding domain (RBD) spike (S) protein SARS-CoV-2. Although there is currently no vaccine, it likely that antibodies will be essential for protection. However, little known about human antibody response SARS-CoV-21–5. Here we report 149...
During B lymphocyte development, antibodies are assembled by random gene segment reassortment to produce a vast number of specificities. A potential disadvantage this process is that some the produced self-reactive. We determined prevalence self-reactive antibody formation and its regulation in human cells. majority (55 75%) all expressed early immature cells displayed self-reactivity, including polyreactive anti-nuclear Most these autoantibodies were removed from population at two discrete...
Dendritic cells (DCs) have the capacity to initiate immune responses, but it has been postulated that they may also be involved in inducing peripheral tolerance. To examine function of DCs steady state we devised an antigen delivery system targeting these specialized presenting vivo using a monoclonal antibody DC-restricted endocytic receptor, DEC-205. Our experiments show this route is several orders magnitude more efficient than free peptide complete Freund's adjuvant (CFA) T cell...
The coronavirus disease 2019 (COVID-19) pandemic presents an urgent health crisis. Human neutralizing antibodies that target the host ACE2 receptor-binding domain (RBD) of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike protein
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected 78 million individuals and is responsible for over 1.7 deaths to date. Infection associated with the development of variable levels antibodies neutralizing activity, which can protect against infection in animal models1,2. Antibody decrease time, but, our knowledge, nature quality memory B cells that would be required produce upon reinfection not been examined. Here we report on humoral response a cohort 87 assessed at...
Here we report on the antibody and memory B cell responses of a cohort 20 volunteers who received Moderna (mRNA-1273) or Pfizer-BioNTech (BNT162b2) vaccine against SARS-CoV-21-4. Eight weeks after second injection vaccine, showed high levels IgM IgG anti-SARS-CoV-2 spike protein (S) receptor-binding-domain (RBD) binding titre. Moreover, plasma neutralizing activity relative numbers RBD-specific cells vaccinated were equivalent to those individuals had recovered from natural infection5,6....
Neutralizing antibodies elicited by prior infection or vaccination are likely to be key for future protection of individuals and populations against SARS-CoV-2. Moreover, passively administered among the most promising therapeutic prophylactic anti-SARS-CoV-2 agents. However, degree which SARS-CoV-2 will adapt evade neutralizing is unclear. Using a recombinant chimeric VSV/SARS-CoV-2 reporter virus, we show that functional S protein variants with mutations in receptor-binding domain (RBD)...
Dendritic cells (DCs) process and present self foreign antigens to induce tolerance or immunity. In vitro models suggest that induction of immunity is controlled by regulating the presentation antigen, but little known about how DCs control antigen in vivo. To examine processing vivo, we specifically targeted two major subsets using chimeric monoclonal antibodies. Unlike CD8 + express cell surface protein CD205, – DCs, which are positive for 33D1 specialized on histocompatibility complex...
Higher order chromatin structure presents a barrier to the recognition and repair of DNA damage. Double-strand breaks (DSBs) induce histone H2AX phosphorylation, which is associated with recruitment factors damaged DNA. To help clarify physiological role H2AX, we targeted in mice. Although not essential for irradiation-induced cell-cycle checkpoints, H2AX-/- mice were radiation sensitive, growth retarded, immune deficient, mutant males infertile. These pleiotropic phenotypes chromosomal...
To identify endocytic receptors that allow dendritic cells (DCs) to capture and present antigens on major histocompatibility complex (MHC) class I products in vivo, we evaluated DEC-205, which is abundant DCs lymphoid tissues. Ovalbumin (OVA) protein, when chemically coupled monoclonal αDEC-205 antibody, was presented by CD11c+ lymph node DCs, but not CD11c− cells, OVA-specific, CD4+ CD8+ T cells. Receptor-mediated presentation at least 400 times more efficient than unconjugated OVA and, for...
Designer Anti-HIV Developing a protective HIV vaccine remains top global health priority. One strategy to identify potential candidates is isolate broadly neutralizing antibodies from infected individuals and then attempt elicit the same antibody response through vaccination (see Perspective by Burton Weiss ). Wu et al. (p. 856 , published online 8 July) now report identification of three antibodies, isolated an HIV-1–infected individual, that exhibited great breadth potency neutralization...
Passive transfer of broadly neutralizing HIV antibodies can prevent infection, which suggests that vaccines elicit such would be protective. Thus far, however, few occur naturally have been characterized. To determine whether these are part a larger group related molecules, we cloned 576 new from four unrelated individuals. All individuals produced expanded clones potent CD4-binding-site mimic binding to CD4. Despite extensive hypermutation, the shared consensus sequence 68 immunoglobulin H...
Dendritic cells (DCs) in lymphoid tissue arise from precursors that also produce monocytes and plasmacytoid DCs (pDCs). Where DC monocyte lineage commitment occurs the nature of precursor migrates bone marrow to peripheral organs are unknown. We show development progresses macrophage common give rise pDCs classical spleen (cDCs), but not monocytes, finally committed cDCs (pre-cDCs). Pre-cDCs enter lymph nodes through migrate along high endothelial venules later disperse integrate into...
Neutralizing antibody responses to coronaviruses mainly target the receptor-binding domain (RBD) of trimeric spike. Here, we characterized polyclonal immunoglobulin Gs (IgGs) and Fabs from COVID-19 convalescent individuals for recognition coronavirus spikes. Plasma IgGs differed in their focus on RBD epitopes, alpha- beta-coronaviruses, contributions avidity increased binding/neutralization over Fabs. Using electron microscopy, examined specificities plasma Fabs, revealing both S1A epitopes...