A5037385564- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- HIV Research and Treatment
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Diabetes and associated disorders
- Monoclonal and Polyclonal Antibodies Research
- Cancer Immunotherapy and Biomarkers
- Immunodeficiency and Autoimmune Disorders
- Viral gastroenteritis research and epidemiology
- Hepatitis B Virus Studies
- Viral Infections and Immunology Research
- Viral Infections and Vectors
- Respiratory viral infections research
- Glycosylation and Glycoproteins Research
- Single-cell and spatial transcriptomics
- Blood groups and transfusion
- Viral Infections and Outbreaks Research
- Immune responses and vaccinations
- Systemic Lupus Erythematosus Research
- vaccines and immunoinformatics approaches
- HIV/AIDS drug development and treatment
- Carbohydrate Chemistry and Synthesis
- Animal Virus Infections Studies
- Hepatitis C virus research
Merck & Co., Inc., Rahway, NJ, USA (United States)
2022-2025
Translational Therapeutics (United States)
2019-2023
University of Pennsylvania
2016-2023
United States Military Academy
2022-2023
Philadelphia University
2023
National Institute of Allergy and Infectious Diseases
2013-2016
National Institutes of Health
2012-2015
Antibodies block Ebola virus entry The recent outbreak in West Africa illustrates the need for both an effective vaccine and therapies to treat infected individuals. Corti et al. isolated two monoclonal antibodies from a survivor of 1995 Kikwit demonstrated their therapeutic efficacy virus–infected macaques. In fact, one antibody protected macaques when it was given up 5 days after infection. Misasi solved crystal structures fragments bound glycoprotein (GP), which mediates viral cell entry....
ABSTRACT The epitopes defined by HIV-1 broadly neutralizing antibodies (bNAbs) are valuable templates for vaccine design, and studies of the immunological development these providing insights vaccination strategies. In addition, most potent reactive bNAbs have potential clinical use. We previously described a family 12 V1V2-directed antibodies, CAP256-VRC26, isolated from an clade C-infected donor at years 1, 2, 4 infection (N. A. Doria-Rose et al., Nature 509:55–62, 2014,...
Serum characterization and antibody isolation are transforming our understanding of the humoral immune response to viral infection. Here, we show that epitope specificities HIV-1-neutralizing antibodies in serum can be elucidated from pattern neutralization against a diverse panel HIV-1 isolates. We determined "neutralization fingerprints" for 30 neutralizing on 34 strains showed similarity fingerprint correlated with epitope. used these fingerprints delineate polyclonal sera 24...
Abstract The role of Ab and B cells in preventing infection is established. In contrast, the cell responses containing chronic infections remains poorly understood. IgG2a (IgG1 humans) can prevent acute infections, T-bet promotes isotype switching. However, whether cell–expressed influence host–pathogen balance during persisting unclear. We demonstrate that cell–specific loss prevents control viral infection. controlled production, as well mucosal localization, proliferation, glycosylation,...
The transcription factors T-bet and Eomesodermin (Eomes) regulate CD8 T cell exhaustion through undefined mechanisms. Here, we show that the subcellular localization of Eomes dictate their regulatory activity in exhausted cells (TEXs). TEXs had a higher ratio nuclear Eomes:T-bet than memory (TMEMs) during chronic lymphocytic choriomeningitis virus (LCMV) infection preclinical cancer models human tumors. Biochemically, compete for same DNA sequences, including Pdcd1 T-box. High strongly...
Identifying molecular mechanisms of exhausted CD8 T cells (T ex ) is a key goal improving immunotherapy cancer and other diseases. However, high-throughput interrogation in vivo can be costly inefficient. In vitro models are easily customizable quickly generate high cellular yield, enabling CRISPR screening assays. We established an model chronic stimulation benchmarked phenotypic, functional, transcriptional, epigenetic features against bona fide . leveraged this combination with to...
ABSTRACT Antibody PG9 is a prototypical member of class V1/V2-directed antibodies that effectively neutralizes diverse strains HIV-1. We analyzed strain-specific resistance to using sequence and structural information. For multiply resistant strains, mutations in short segment V1/V2 resulted gain sensitivity related neutralizing antibodies, suggesting both common mechanism HIV-1 mode recognition by this antibodies.
Background/Objectives: The respiratory syncytial virus (RSV) is a major cause of lower tract infections in children and adults. With nearly everyone infected by the age five, there an opportunity to develop booster vaccines that enhance B-cell immunity, promoting potent broadly neutralizing antibodies. One potential approach involves using anti-idiotypic antibodies (anti-IDs) mimic specific antigenic sites preexisting immunity epitope-specific manner. RB1, monoclonal antibody (mAb) binds...
Background/Objectives: Mucosal vaccines are rare but commercially desirable because of their real and theoretical biological advantages. Spores vegetative forms from Bacillus have been used as probiotics due to stability under various environmental conditions, including heat, gastric acidity, moisture. Preclinical studies shown that subtilis (B. subtilis) spores can serve effective mucosal adjuvants. Our study aimed evaluate B. a adjuvant. Methods Results: We demonstrate in rodents the...
Abstract In response to infection or immunization, antibodies are produced that provide protection against re-exposure with the same pathogen. These can persist at high titers for decades and maintained by bone marrow-resident long-lived plasma cells (LLPC). However, durability of antibody responses immunization varies amongst vaccines. It is unknown what factors contribute differential longevity serum whether heterogeneity in LLPC contributes this phenomenon. While differentiation has been...
Abstract Background Clesrovimab is a human half-life extended mAb in phase 3 evaluation for the prevention of RSV disease infants. ADA were observed at late time points 1b/2a study where clesrovimab was well tolerated with an ∼45 days. Methods Serum samples days 150, 365 and 545 post-dose assayed titers. Samples high titers characterized their binding specificity to Fab or YTE portion clesrovimab. serum neutralization (SNA) also measured on ADA+ ADA- Additionally, D25 (site Ø) competitive...
Abstract Naïve CD8 T cells can differentiate into effector (T EFF ), memory MEM or exhausted EX ) cells. These developmental pathways are associated with distinct transcriptional and epigenetic changes that endow different functional capacities therefore therapeutic potential. The molecular circuitry underlying these trajectories the extent of heterogeneity within , populations remain poorly understood. Here, we used lymphocytic choriomeningitis virus model acutely-resolved chronic infection...
Identifying novel molecular mechanisms of exhausted CD8 T cells (T
SUMMARY Chronic viral infections disrupt B cell responses leading to impaired affinity maturation and delayed control of viremia. Previous studies have identified early pre-germinal center (GC) attrition but the impact chronic on fate decisions in GC remains poorly understood. To address this question, we used single-cell transcriptional profiling virus-specific cells test hypothesis that infection disrupted suboptimal humoral immunity. These revealed a critical differentiation checkpoint is...
Abstract Human immunodeficiency virus (HIV) and hepatitis C (HCV) are chronic viral infections that cause significant morbidity mortality worldwide. Current efforts to vaccinate against these pathogens have been unsuccessful failed induce effective neutralizing antibodies capable of mediating sterilizing immunity. Natural HIV HCV infection elicits the production affinity matured class-switched target proteins. While can drive evolution, they ineffective at controlling infection. Moreover, it...
Background Antibody PG9 is a prototypical member of class V1/V2-directed antibodies that effectively neutralizes diverse strains HIV-1. The crystal structure bound to scaffolded V1/V2 has provided insight into its mode recognition. We sought gain more complete understanding the interaction with functional viral spike, and extend our other this class. Methods analyzed amino acid frequencies in V2 region sensitive resistant identify potentially important residues. also used potential contact...