A5057578475- SARS-CoV-2 and COVID-19 Research
- COVID-19 Clinical Research Studies
- Immunodeficiency and Autoimmune Disorders
- Chronic Lymphocytic Leukemia Research
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- SARS-CoV-2 detection and testing
- Diabetes and associated disorders
- Influenza Virus Research Studies
- Immunotherapy and Immune Responses
- COVID-19 epidemiological studies
- Vibrio bacteria research studies
- Immune responses and vaccinations
- Escherichia coli research studies
- Pancreatic function and diabetes
- Long-Term Effects of COVID-19
- Lymphoma Diagnosis and Treatment
- Phagocytosis and Immune Regulation
- Respiratory viral infections research
- IL-33, ST2, and ILC Pathways
- Eosinophilic Esophagitis
- Parasites and Host Interactions
- HIV Research and Treatment
- Inflammatory mediators and NSAID effects
- COVID-19 Impact on Reproduction
Emory University
2020-2023
Children's Healthcare of Atlanta
2020-2023
Vanderbilt University Medical Center
2017-2022
Vanderbilt University
2015-2021
Emory National Primate Research Center
2021
University of Georgia
2013
SARS-CoV-2, the virus responsible for COVID-19, is causing a devastating worldwide pandemic, and there pressing need to understand development, specificity, neutralizing potency of humoral immune responses during acute infection. We report cross-sectional study antibody receptor-binding domain (RBD) spike protein neutralization activity in cohort 44 hospitalized COVID-19 patients. RBD-specific IgG are detectable all patients 6 days after PCR confirmation. Isotype switching occurs rapidly,...
Ending the COVID-19 pandemic will require long-lived immunity to SARS-CoV-2. Here, we evaluate 254 patients longitudinally up 8 months and find durable broad-based immune responses. SARS-CoV-2 spike binding neutralizing antibodies exhibit a bi-phasic decay with an extended half-life of >200 days suggesting generation longer-lived plasma cells. infection also boosts antibody titers SARS-CoV-1 common betacoronaviruses. In addition, spike-specific IgG+ memory B cells persist, which bodes well...
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) omicron variant emerged in November 2021 and consists of several mutations within the spike. We use serum from mRNA-vaccinated individuals to measure neutralization activity against a live-virus assay. At 2-4 weeks after primary series vaccinations, we observe 30-fold reduction neutralizing omicron. Six months initial two-vaccine doses, sera naive vaccinated subjects show no In contrast, COVID-19-recovered 6 receiving...
SARS-CoV-2 is currently causing a devastating pandemic and there pressing need to understand the dynamics, specificity, neutralizing potency of humoral immune response during acute infection. Herein, we report dynamics antibody responses receptor-binding domain (RBD) spike protein virus neutralization activity in 44 COVID-19 patients. RBD-specific IgG were detectable all patients 6 days after PCR confirmation. Using clinical isolate SARS-CoV-2, titers also The magnitude binding correlated...
SUMMARY Ending the COVID-19 pandemic will require long-lived immunity to SARS-CoV-2. Here, we evaluate 254 patients longitudinally up eight months and find durable broad-based immune responses. SARS-CoV-2 spike binding neutralizing antibodies exhibit a bi-phasic decay with an extended half-life of >200 days suggesting generation longer-lived plasma cells. infection also boosts antibody titers SARS-CoV-1 common betacoronaviruses. In addition, spike-specific IgG+ memory B cells persist,...
The emergence of SARS-CoV-2 variants with mutations in the spike protein is raising concerns about efficacy infection- or vaccine-induced antibodies to neutralize these variants. We compared antibody binding and live virus neutralization sera from naturally infected mRNA vaccinated individuals against a circulating B.1 variant emerging B.1.351 variant. In acutely-infected (5-19 days post-symptom onset), convalescent COVID-19 (through 8 months onset) mRNA-1273 (day 14 post-second dose), we...
The ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic highlights the importance of determining breadth and durability humoral immunity to SARS-CoV-2 mRNA vaccination. Herein, we characterize response in 27 naive 40 recovered vaccinees. SARS-CoV-2-specific antibody memory B cell (MBC) responses are durable up 6 months, although half-lives shorter for recipients. magnitude vaccination strongly correlates with initial infection. Neutralization titers lower against...
To examine COVID-19 mRNA vaccine-induced binding and neutralizing antibody responses in patients with non-small-cell lung cancer (NSCLC) to SARS-CoV-2 614D (wild type [WT]) strain variants of concern after the primary 2-dose booster vaccination.
Abstract The BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) vaccines generate potent neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the global emergence of SARS-CoV-2 variants with mutations in spike protein, principal antigenic target these vaccines, has raised concerns over activity vaccine-induced antibody responses. Omicron variant, which emerged November 2021, consists 30 within protein. Here, we used an authentic live virus...
As SARS-CoV-2 becomes endemic, it is critical to understand immunity following early-life infection. We evaluated humoral responses in 23 infants/young children. Antibody spike antigens peaked approximately 30 days after infection and were maintained up 500 with little apparent decay. While the magnitude of was similar an adult cohort recovered from mild/moderate COVID-19, both binding neutralization titers WT more durable children, RBD IgG antibody half-life nearly 4X as long adults....
Abstract Bruton’s tyrosine kinase (Btk) is a crucial regulator of B cell signaling and therapeutic target for lymphoma autoimmune disease. BTK-deficient patients suffer from humoral immunodeficiency, as their cells fail to progress beyond the bone marrow. However, role Btk in fully developed, mature peripheral not well understood. Analysis using BTK inhibitors complicated by suboptimal inhibition, off-target effects, or failure eliminate BTK’s adaptor function. Therefore Btkflox/Cre-ERT2...
Abstract IL-33 is an IL-1 family member protein that a potent driver of inflammatory responses in both allergic and nonallergic disease. This proinflammatory effect mediated primarily by extracellular release from stromal cells binding the C-terminal domain to its receptor ST2 on targets such as CD4+ Th2 cells, ILC2, mast cells. Notably, has distinct N-terminal mediates nuclear localization chromatin binding. However, defined vivo cell-intrinsic role for not been established. We identified...
Objective Bruton's tyrosine kinase (BTK) is a B cell signaling protein that also contributes to innate immunity. BTK inhibitors prevent autoimmune arthritis but have off‐target effects, and the mechanisms of protection remain unknown. We undertook these studies using genetic deletion investigate role in adaptive immune responses drive inflammatory arthritis. Methods BTK‐deficient K/BxN mice were generated study spontaneous model requires both The serum‐transfer was used bypass system...
The integration of inflammatory signals is paramount in controlling the intensity and duration immune responses. Eicosanoids, particularly PGE2, are critical molecules initiation resolution inflammation transition from innate to acquired Microsomal PGE synthase 1 (mPGES1) an integral membrane enzyme whose regulated expression controls PGE2 levels highly expressed at sites inflammation. also associated with modulation autoimmunity through altering IL-23/IL-17 axis regulatory T cell (Treg)...
We investigated SARS-CoV-2 mRNA vaccine-induced binding and live-virus neutralizing antibody response in NSCLC patients to the wild type strain emerging Delta Omicron variants.82 53 healthy adult volunteers who received vaccines were included study. Blood was collected longitudinally, SARS-CoV-2-specific neutralization 614D (WT), B.1.617.2 (Delta), B.1.351 (Beta) B.1.1.529 (Omicron) variants evaluated by Meso Scale Discovery (MSD) assay Focus Reduction Neutralization Assay (FRNT)...
Bruton's tyrosine kinase (Btk) deficiency preferentially eliminates autoreactive B cells while sparing normal humoral responses, but has not been studied in mucosal immunity. Commensal microbes and intact BTK signaling have independently shown to be essential for arthritis development K/BxN mice. Here, we examine how BTK-mediated interfaces with the gut microbiome. Btk-deficient mice were found small Peyer's Patches reduced germinal center IgA class-switched cells. IgA-switched plasma...
Expansion of autoimmune-prone marginal zone (MZ) B cells has been implicated in type 1 diabetes. To test disease contributions MZ NOD mice, Notch2 haploinsufficiency (Notch2(+/-)) was introduced but failed to eliminate the MZ, as it does C57BL/6 mice. Notch2(+/-)/NOD have cell numbers similar those wild-type C57BL/6, yet still develop whether BCR signaling supports cells, Bruton's tyrosine kinase (Btk) deficiency introduced. Surprisingly, Btk-deficient Expression and its transcriptional...
Immunity to the severe diarrheal disease cholera is largely mediated by lipopolysaccharide (LPS)-specific antibodies. However, properties and protective mechanism of functionally relevant antibodies have not been well defined.
The factors that control the development of an effective immune response to recently emerged SARS-CoV-2 virus are poorly understood. In this study, we provide a cross-sectional analysis dynamics B cell responses infection in hospitalized COVID-19 patients. We observe changes subsets consistent with robust humoral response, including significant expansion plasmablasts and activated receptor-binding domain (RBD)-specific memory populations. elevated titers Abs RBD, full-length Spike,...
Signaling lymphocytic activation molecule-associated protein (SAP), a critical intracellular signaling molecule for T-B lymphocyte interactions, drives T follicular helper (Tfh) cell development in germinal centers (GCs). High-affinity islet autoantibodies predict type 1 diabetes (T1D) but do not cause β destruction. This paradox intimates Tfh cells as key pathologic effectors, consistent with an observed signature T1D. To understand how fully developed (GC Tfh) contribute to different...
Abstract Bruton’s tyrosine kinase (Btk) propagates B cell signaling, and BTK inhibitors are in clinical trials for autoimmune disease. Although autoreactive cells fail to develop the absence of Btk, its role mature is unknown. To address this issue, a model conditional removal (Btkflox/Cre-ERT2) was used excise Btk from transgenic that recognize pathophysiologic autoantigen insulin. Anti-insulin escape central tolerance promote diabetes, mimicking human cells. Lifelong deficiency previously...
The dynamics of innate and adaptive immunity to infection in infants remain obscure. Here, we used a multi-omics approach perform longitudinal analysis SARS-CoV-2 young children the first weeks months life by analyzing blood samples collected before, during, after with Omicron Non-Omicron variants. Infection stimulated robust antibody titers that, unlike adults, were stably maintained for >300 days. Antigen-specific memory B cell (MCB) responses durable 150 days but waned thereafter. Somatic...