Ebola virus (EBOV) remains a public health threat. We performed a longitudinal study of B cell responses to EBOV in four survivors of the 2014 West African outbreak. Infection induced lasting ...EBOV-specific immunoglobulin G (IgG) antibodies, but their subclass composition changed over time, with IgG1 persisting, IgG3 rapidly declining, and IgG4 appearing late. Striking changes occurred in the immunoglobulin repertoire, with massive recruitment of naive B cells that subsequently underwent hypermutation. We characterized a large panel of EBOV glycoprotein-specific monoclonal antibodies (mAbs). Only a small subset of mAbs that bound glycoprotein by ELISA recognized cell-surface glycoprotein. However, this subset contained all neutralizing mAbs. Several mAbs protected against EBOV disease in animals, including one mAb that targeted an epitope under evolutionary selection during the 2014 outbreak. Convergent antibody evolution was seen across multiple donors, particularly among VH3-13 neutralizing antibodies specific for the GP1 core. Our study provides a benchmark for assessing EBOV vaccine-induced immunity.
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•Ebola virus infection causes massive recruitment of naive B cells•Virus-specific antibodies continue to class-switch and mutate for months after acute infection•Protective antibodies can be neutralizing or non-neutralizing and can appear early•Convergent, protective antibody rearrangements are seen in multiple donors
A longitudinal study of Ebola virus infection survivors maps out the antibody features that confer protection, with potential implications for vaccination.
SARS-CoV-2-specific antibodies, particularly those preventing viral spike receptor binding domain (RBD) interaction with host angiotensin-converting enzyme 2 (ACE2) receptor, can neutralize the ...virus. It is, however, unknown which features of the serological response may affect clinical outcomes of COVID-19 patients. We analyzed 983 longitudinal plasma samples from 79 hospitalized COVID-19 patients and 175 SARS-CoV-2-infected outpatients and asymptomatic individuals. Within this cohort, 25 patients died of their illness. Higher ratios of IgG antibodies targeting S1 or RBD domains of spike compared to nucleocapsid antigen were seen in outpatients who had mild illness versus severely ill patients. Plasma antibody increases correlated with decreases in viral RNAemia, but antibody responses in acute illness were insufficient to predict inpatient outcomes. Pseudovirus neutralization assays and a scalable ELISA measuring antibodies blocking RBD-ACE2 interaction were well correlated with patient IgG titers to RBD. Outpatient and asymptomatic individuals' SARS-CoV-2 antibodies, including IgG, progressively decreased during observation up to five months post-infection.
Adaptive immune responses in humans rely on somatic genetic rearrangements of Ig and T-cell receptor loci to generate diverse antigen receptors. It is unclear to what extent an individual’s genetic ...background affects the characteristics of the antibody repertoire used in responding to vaccination or infection. We studied the B-cell repertoires and clonal expansions in response to attenuated varicella-zoster vaccination in four pairs of adult identical twins and found that the global antibody repertoires of twin pair members showed high similarity in antibody heavy chain V, D, and J gene segment use, and in the length and features of the complementarity-determining region 3, a major determinant of antigen binding. These twin similarities were most pronounced in the IgM-expressing B-cell pools, but were seen to a lesser extent in IgG-expressing B cells. In addition, the degree of antibody somatic mutation accumulated in the B-cell repertoire was highly correlated within twin pair members. Twin pair members had greater numbers of shared convergent antibody sequences, including mutated sequences, suggesting similarity among memory B-cell clonal lineages. Despite these similarities in the memory repertoire, the B-cell clones used in acute responses to ZOSTAVAX vaccination were largely unique to each individual. Taken together, these results suggest that the overall B-cell repertoire is significantly shaped by the underlying germ-line genome, but that stochastic or individual-specific effects dominate the selection of clones in response to an acute antigenic stimulus.
Significance Human B cells secrete highly diverse antibody molecules to recognize and defend against infectious agents. Developing B cells independently rearrange their genomes to produce antibody-encoding sequences. It is uncertain to what degree genetic factors control antibody repertoires and the antibodies elicited by defined antigenic stimuli. Analysis of 134,000 antibody heavy chain sequences from genetically identical twins vaccinated with varicella-zoster vaccine indicates that twins show increased correlation in antibody gene segment usage, junctional features, and mutation rates in their antibody pools but show little similarity in clonal responses to an acute stimulus. Therefore, a shared germ-line genome sequence is correlated with overall convergence of antibody repertoires, but the particular antibody response to a given vaccination is less predictable.
In the past few decades, the prevalence of allergic diseases has increased worldwide. Here, we review the etiology and pathophysiology of allergic diseases, including the role of the epithelial ...barrier, the immune system, climate change, and pollutants. Our current understanding of the roles of early life and infancy; diverse diet; skin, respiratory, and gut barriers; and microbiome in building immune tolerance to common environmental allergens has led to changes in prevention guidelines. Recent developments on the mechanisms involved in allergic diseases have been translated to effective treatments, particularly in the past 5 years, with additional treatments now in advanced clinical trials.
Food allergy and omics Dhondalay, Gopal Krishna; Rael, Efren; Acharya, Swati ...
Journal of allergy and clinical immunology,
January 2018, 2018-01-00, 20180101, Letnik:
141, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Food allergy (FA) prevalence has been increasing over the last few decades and is now a global health concern. Current diagnostic methods for FA result in a high number of false-positive results, and ...the standard of care is either allergen avoidance or use of epinephrine on accidental exposure, although currently with no other approved treatments. The increasing prevalence of FA, lack of robust biomarkers, and inadequate treatments warrants further research into the mechanism underlying food allergies. Recent technological advances have made it possible to move beyond traditional biological techniques to more sophisticated high-throughput approaches. These technologies have created the burgeoning field of omics sciences, which permit a more systematic investigation of biological problems. Omics sciences, such as genomics, epigenomics, transcriptomics, proteomics, metabolomics, microbiomics, and exposomics, have enabled the construction of regulatory networks and biological pathway models. Parallel advances in bioinformatics and computational techniques have enabled the integration, analysis, and interpretation of these exponentially growing data sets and opens the possibility of personalized or precision medicine for FA.
T cells are a critical component of the response to SARS-CoV-2, but their kinetics after infection and vaccination are insufficiently understood. Using “spheromer” peptide-MHC multimer reagents, we ...analyzed healthy subjects receiving two doses of the Pfizer/BioNTech BNT162b2 vaccine. Vaccination resulted in robust spike-specific T cell responses for the dominant CD4+ (HLA-DRB1∗15:01/S191) and CD8+ (HLA-A∗02/S691) T cell epitopes. Antigen-specific CD4+ and CD8+ T cell responses were asynchronous, with the peak CD4+ T cell responses occurring 1 week post the second vaccination (boost), whereas CD8+ T cells peaked 2 weeks later. These peripheral T cell responses were elevated compared with COVID-19 patients. We also found that previous SARS-CoV-2 infection resulted in decreased CD8+ T cell activation and expansion, suggesting that previous infection can influence the T cell response to vaccination.
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•CD8+ and CD4+ T cell responses characterized using SARS-CoV-2 pMHC spheromers•CD8+ and CD4+ T cell response kinetics are decoupled after mRNA vaccination•Reduced peripheral CD8+ T cell responses after infection compared with mRNA vaccination•Previous exposure limits peripheral CD8+ T cell responses after mRNA vaccination
Our understanding of T cell responses in COVID-19 and vaccination is incomplete. Gao et al. examine SARS-CoV-2-specific T cell responses to infection and vaccination, revealing disparate kinetics between CD4+ and CD8+ T cells. Furthermore, compared with vaccination alone, circulating CD8+ T cells are attenuated during infection and in subsequent vaccination.
Abstract
Objectives
Kikuchi-Fujimoto disease (KFD) and systemic lupus erythematosus (SLE) are benign entities with histologic features that raise concern about malignancy and infection. We searched ...for a histology-independent KFD/SLE signature relying on only immunophenotype and basic clinical characteristics.
Methods
A histology-independent KFD/SLE signature was generated using 975 excised lymph nodes with flow immunophenotyping, including 16 cases of KFD/SLE. This signature was then evaluated in 1,198 fine-needle aspiration (FNA) specimens.
Results
The top flow cytometry discriminant for KFD/SLE was uniform CD38+ expression on CD19+ events. Immunohistochemistry demonstrated nodules of IgD+, IgM− B cells surrounding necrotizing and activated T-cell areas. A signature combining 6 flow cytometry criteria with age and sample site had a positive predictive value of 88% for KFD/SLE, which had a prevalence of 1.6%. All 4 signature-positive FNA cases with follow-up excision were KFD/SLE. At a second institution, 4 of 5 KFD/SLE cases passed the top discriminant.
Conclusions
A flow cytometry signature combined with age and biopsy site identifies KFD/SLE independent of histology, suggesting a shared immune composition and independently confirming that KFD/SLE represents a distinct entity. Unexpectedly, an IgD+CD38+ small B-cell population is a distinctive feature of KFD/SLE, suggesting a possible pathologic role for anergic/autoreactive B cells.
The gastrointestinal mucosa is a critical environmental interface where plasma cells and B cells are exposed to orally-ingested antigens such as food allergen proteins. It is unclear how the ...development of B cells and plasma cells in the gastrointestinal mucosa differs between healthy humans and those with food allergy, and how B cells contribute to, or are affected by, the breakdown of oral tolerance. In particular, the antibody gene repertoires associated with symptomatic allergy have only begun to be characterized in full molecular detail. Here, we review literature concerning B cells and plasma cells in the gastrointestinal system in the context of food allergy, with a focus on human studies.
The supply and bioavailability of dissolved iron sets the magnitude of surface productivity for ∼40% of the global ocean. The redox state, organic complexation, and phase (dissolved versus ...particulate) of iron are key determinants of iron bioavailability in the marine realm, although the mechanisms facilitating exchange between iron species (inorganic and organic) and phases are poorly constrained. Here we use the isotope fingerprint of dissolved and particulate iron to reveal distinct isotopic signatures for biological uptake of iron during a GEOTRACES process study focused on a temperate spring phytoplankton bloom in subtropical waters. At the onset of the bloom, dissolved iron within the mixed layer was isotopically light relative to particulate iron. The isotopically light dissolved iron pool likely results from the reduction of particulate iron via photochemical and (to a lesser extent) biologically mediated reduction processes. As the bloom develops, dissolved iron within the surface mixed layer becomes isotopically heavy, reflecting the dominance of biological processing of iron as it is removed from solution, while scavenging appears to play a minor role. As stable isotopes have shown for major elements like nitrogen, iron isotopes offer a new window into our understanding of the biogeochemical cycling of iron, thereby allowing us to disentangle a suite of concurrent biotic and abiotic transformations of this key biolimiting element.
Significance The supply and bioavailability of dissolved iron sets the magnitude of surface productivity for approximately 40% of the global ocean; however, our knowledge of how it is transferred between chemical states and pools is poorly constrained. Here we utilize the isotopic composition of dissolved and particulate iron to fingerprint its transformation in the surface ocean by abiotic and biotic processes. Photochemical and biological reduction and dissolution of particulate iron in the surface ocean appear to be key processes in regulating its supply and bioavailability to marine biota. Iron isotopes offer a new window into our understanding of the internal cycling of Fe, thereby allowing us to follow its biogeochemical transformations in the surface ocean.
Monoclonal antibodies derived from blood plasma cells of acute HIV-1-infected individuals are predominantly targeted to the HIV Env gp41 and cross-reactive with commensal bacteria. To understand this ...phenomenon, we examined anti-HIV responses in ileum B cells using recombinant antibody technology and probed their relationship to commensal bacteria. The dominant ileum B cell response was to Env gp41. Remarkably, a majority (82%) of the ileum anti-gp41 antibodies cross-reacted with commensal bacteria, and of those, 43% showed non-HIV-1 antigen polyreactivity. Pyrosequencing revealed shared HIV-1 antibody clonal lineages between ileum and blood. Mutated immunoglobulin G antibodies cross-reactive with both Env gp41 and microbiota could also be isolated from the ileum of HIV-1 uninfected individuals. Thus, the gp41 commensal bacterial antigen cross-reactive antibodies originate in the intestine, and the gp41 Env response in HIV-1 infection can be derived from a preinfection memory B cell pool triggered by commensal bacteria that cross-react with Env.
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•HIV-1-reactive B cells in the terminal ileum primarily target Env gp41•A majority of the HIV-1 gp41-reactive antibodies cross- react with commensal bacteria•B cell clonal lineages are shared between the terminal ileum and blood•Env gp41 and microbiota cross-reactive IgG can be isolated from HIV-1 naive individuals
The initial, nonneutralizing antibody response to HIV-1 may derive from memory B cells cross-reactive with environmental antigens. By isolating antibodies from ileum B cells, Trama et al. provide evidence that a preinfection pool of microbiota-reactive B cells can be the origin of the antibody response to acute HIV-1 infection.
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