Publications by authors named "Sandra C A Nielsen"

13 Publications

  • Page 1 of 1

mRNA vaccination compared to infection elicits an IgG-predominant response with greater SARS-CoV-2 specificity and similar decrease in variant spike recognition.

medRxiv 2021 Apr 7. Epub 2021 Apr 7.

During the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, new vaccine strategies including lipid nanoparticle delivery of antigen encoding RNA have been deployed globally. The BioNTech/Pfizer mRNA vaccine BNT162b2 encoding SARS-CoV-2 spike protein shows 95% efficacy in preventing disease, but it is unclear how the antibody responses to vaccination differ from those generated by infection. Here we compare the magnitude and breadth of antibodies targeting SARS-CoV-2, SARS-CoV-2 variants of concern, and endemic coronaviruses, in vaccinees and infected patients. We find that vaccination differs from infection in the dominance of IgG over IgM and IgA responses, with IgG reaching levels similar to those of severely ill COVID-19 patients and shows decreased breadth of the antibody response targeting endemic coronaviruses. Viral variants of concern from B.1.1.7 to P.1 to B.1.351 form a remarkably consistent hierarchy of progressively decreasing antibody recognition by both vaccinees and infected patients exposed to Wuhan-Hu-1 antigens.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1101/2021.04.05.21254952DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8043478PMC
April 2021

Shared B cell memory to coronaviruses and other pathogens varies in human age groups and tissues.

Science 2021 May 12;372(6543):738-741. Epub 2021 Apr 12.

Department of Pathology, Stanford University, Stanford, CA 94305, USA.

Vaccination and infection promote the formation, tissue distribution, and clonal evolution of B cells, which encode humoral immune memory. We evaluated pediatric and adult blood and deceased adult organ donor tissues to determine convergent antigen-specific antibody genes of similar sequences shared between individuals. B cell memory varied for different pathogens. Polysaccharide antigen-specific clones were not exclusive to the spleen. Adults had higher clone frequencies and greater class switching in lymphoid tissues than blood, while pediatric blood had abundant class-switched convergent clones. Consistent with reported serology, prepandemic children had class-switched convergent clones to severe acute respiratory syndrome coronavirus 2 with weak cross-reactivity to other coronaviruses, while adult blood or tissues showed few such clones. These results highlight the prominence of early childhood B cell clonal expansions and cross-reactivity for future responses to novel pathogens.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1126/science.abf6648DOI Listing
May 2021

Reinfection with SARS-CoV-2 and Failure of Humoral Immunity: a case report.

medRxiv 2020 Sep 25. Epub 2020 Sep 25.

Recovery from COVID-19 is associated with production of anti-SARS-CoV-2 antibodies, but it is uncertain whether these confer immunity. We describe viral RNA shedding duration in hospitalized patients and identify patients with recurrent shedding. We sequenced viruses from two distinct episodes of symptomatic COVID-19 separated by 144 days in a single patient, to conclusively describe reinfection with a new strain harboring the spike variant D614G. With antibody and B cell analytics, we show correlates of adaptive immunity, including a differential response to D614G. Finally, we discuss implications for vaccine programs and begin to define benchmarks for protection against reinfection from SARS-CoV-2.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1101/2020.09.22.20192443DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7523175PMC
September 2020

Human B Cell Clonal Expansion and Convergent Antibody Responses to SARS-CoV-2.

Cell Host Microbe 2020 10 3;28(4):516-525.e5. Epub 2020 Sep 3.

Department of Pathology, Stanford University, Stanford, CA 94305, USA; Sean N. Parker Center for Allergy and Asthma Research, Stanford University School of Medicine, Stanford, CA, 94305, USA. Electronic address:

B cells are critical for the production of antibodies and protective immunity to viruses. Here we show that patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who develop coronavirus disease 2019 (COVID-19) display early recruitment of B cells expressing a limited subset of IGHV genes, progressing to a highly polyclonal response of B cells with broader IGHV gene usage and extensive class switching to IgG and IgA subclasses with limited somatic hypermutation in the initial weeks of infection. We identify convergence of antibody sequences across SARS-CoV-2-infected patients, highlighting stereotyped naive responses to this virus. Notably, sequence-based detection in COVID-19 patients of convergent B cell clonotypes previously reported in SARS-CoV infection predicts the presence of SARS-CoV/SARS-CoV-2 cross-reactive antibody titers specific for the receptor-binding domain. These findings offer molecular insights into shared features of human B cell responses to SARS-CoV-2 and SARS-CoV.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chom.2020.09.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7470783PMC
October 2020

B cell clonal expansion and convergent antibody responses to SARS-CoV-2.

Res Sq 2020 May 6. Epub 2020 May 6.

Department of Pathology, Stanford University.

During virus infection B cells are critical for the production of antibodies and protective immunity. Establishment of a diverse antibody repertoire occurs by rearrangement of germline DNA at the immunoglobulin heavy and light chain loci to encode the membrane-bound form of antibodies, the B cell antigen receptor. Little is known about the B cells and antigen receptors stimulated by the novel human coronavirus SARS-CoV-2. Here we show that the human B cell compartment in patients with diagnostically confirmed SARS-CoV-2 and clinical COVID-19 is rapidly altered with the early recruitment of B cells expressing a limited subset of V genes, and extensive activation of IgG and IgA subclasses without significant somatic mutation. We detect expansion of B cell clones as well as convergent antibodies with highly similar sequences across SARS-CoV-2 patients, highlighting stereotyped naïve responses to this virus. A shared convergent B cell clonotype in SARS-CoV-2 infected patients was previously seen in patients with SARS. These findings offer molecular insights into shared features of human B cell responses to SARS-CoV-2 and other zoonotic spillover coronaviruses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21203/rs.3.rs-27220/v1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7336706PMC
May 2020

Human B cell clonal expansion and convergent antibody responses to SARS-CoV-2.

bioRxiv 2020 Jul 9. Epub 2020 Jul 9.

Department of Pathology, Stanford University, Stanford, CA 94305, USA.

During virus infection B cells are critical for the production of antibodies and protective immunity. Here we show that the human B cell compartment in patients with diagnostically confirmed SARS-CoV-2 and clinical COVID-19 is rapidly altered with the early recruitment of B cells expressing a limited subset of IGHV genes, progressing to a highly polyclonal response of B cells with broader IGHV gene usage and extensive class switching to IgG and IgA subclasses with limited somatic hypermutation in the initial weeks of infection. We identify extensive convergence of antibody sequences across SARS-CoV-2 patients, highlighting stereotyped naïve responses to this virus. Notably, sequence-based detection in COVID-19 patients of convergent B cell clonotypes previously reported in SARS-CoV infection predicts the presence of SARS-CoV/SARS-CoV-2 cross-reactive antibody titers specific for the receptor-binding domain. These findings offer molecular insights into shared features of human B cell responses to SARS-CoV-2 and other zoonotic spillover coronaviruses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1101/2020.07.08.194456DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7359515PMC
July 2020

Origins and clonal convergence of gastrointestinal IgE B cells in human peanut allergy.

Sci Immunol 2020 03;5(45)

Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.

B cells in human food allergy have been studied predominantly in the blood. Little is known about IgE B cells or plasma cells in tissues exposed to dietary antigens. We characterized IgE clones in blood, stomach, duodenum, and esophagus of 19 peanut-allergic patients, using high-throughput DNA sequencing. IgE cells in allergic patients are enriched in stomach and duodenum, and have a plasma cell phenotype. Clonally related IgE and non-IgE-expressing cell frequencies in tissues suggest local isotype switching, including transitions between IgA and IgE isotypes. Highly similar antibody sequences specific for peanut allergen Ara h 2 are shared between patients, indicating that common immunoglobulin genetic rearrangements may contribute to pathogenesis. These data define the gastrointestinal tract as a reservoir of IgE B lineage cells in food allergy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1126/sciimmunol.aay4209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7691169PMC
March 2020

Longitudinal Analysis of the Human B Cell Response to Ebola Virus Infection.

Cell 2019 05 16;177(6):1566-1582.e17. Epub 2019 May 16.

Emory Vaccine Center and Department of Microbiology and Immunology, Emory University, Atlanta, GA, USA. Electronic address:

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cell.2019.04.036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6908968PMC
May 2019

Shaping of infant B cell receptor repertoires by environmental factors and infectious disease.

Sci Transl Med 2019 02;11(481)

Department of Pathology, Stanford University, Stanford, CA 94305, USA.

Antigenic exposures at epithelial sites in infancy and early childhood are thought to influence the maturation of humoral immunity and modulate the risk of developing immunoglobulin E (IgE)-mediated allergic disease. How different kinds of environmental exposures influence B cell isotype switching to IgE, IgG, or IgA, and the somatic mutation maturation of these antibody pools, is not fully understood. We sequenced antibody repertoires in longitudinal blood samples in a birth cohort from infancy through the first 3 years of life and found that, whereas IgG and IgA show linear increases in mutational maturation with age, IgM and IgD mutations are more closely tied to pathogen exposure. IgE mutation frequencies are primarily increased in children with impaired skin barrier conditions such as eczema, suggesting that IgE affinity maturation could provide a mechanistic link between epithelial barrier failure and allergy development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1126/scitranslmed.aat2004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6733608PMC
February 2019

Human adaptive immune receptor repertoire analysis-Past, present, and future.

Immunol Rev 2018 07;284(1):9-23

Department of Pathology, Stanford University, Stanford, CA, USA.

The genes encoding adaptive immune antigen receptors, namely the immunoglobulins expressed in membrane-bound or secreted forms by B cells, and the cell surface T cell receptors, are unique in human biology because they are generated by combinatorial rearrangement of the genomic DNA. The diversity of receptors so generated in populations of lymphocytes enables the human immune system to recognize antigens expressed by pathogens, but also underlies the pathological specificity of autoimmune diseases and the mistargeted immunity in allergies. Several recent technological developments, foremost among them the invention of high-throughput DNA sequencing instruments, have enabled much deeper and thorough evaluation of clones of human B cells and T cells and the antigen receptors they express during physiological and pathogenic immune responses. The evolutionary struggles between host adaptive immune responses and populations of pathogens are now open to greater scrutiny, elucidation of the underlying reasons for successful or failed immunity, and potential predictive modeling, than ever before. Here we give an overview of the foundations, recent progress, and future prospects in this dynamic area of research.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/imr.12667DOI Listing
July 2018

Recent diversification of a marine genus (Tursiops spp.) tracks habitat preference and environmental change.

Syst Biol 2013 Nov 8;62(6):865-77. Epub 2013 Aug 8.

School of Biological and Biomedical Sciences, Durham University, South Road, DH1 3LE, UK; Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Øster Voldgade 5-7, DK-1350 Copenhagen K, Denmark; Biological Department, UAE University, P.O.Box 17551, Al Ain, UAE; and School of Biological Sciences, Flinders University, GPO Box 2100, Adelaide, South Australia 5001, Australia.

Understanding the evolution of diversity and the resulting systematics in marine systems is confounded by the lack of clear boundaries in oceanic habitats, especially for highly mobile species like marine mammals. Dolphin populations and sibling species often show differentiation between coastal and offshore habitats, similar to the pelagic/littoral or benthic differentiation seen for some species of fish. Here we test the hypothesis that lineages within the polytypic genus Tursiops track past changes in the environment reflecting ecological drivers of evolution facilitated by habitat release. We used a known recent time point for calibration (the opening of the Bosphorus) and whole mitochondrial genome (mitogenome) sequences for high phylogenetic resolution. The pattern of lineage formation suggested an origin in Australasia and several early divisions involving forms currently inhabiting coastal habitats. Radiation in pelagic environments was relatively recent, and was likely followed by a return to coastal habitat in some regions. The timing of some nodes defining different ecotypes within the genus clustered near the two most recent interglacial transitions. A signal for an increase in diversification was also seen for dates after the last glacial maximum. Together these data suggest the tracking of habitat preference during geographic expansions, followed by transition points reflecting habitat shifts, which were likely associated with periods of environmental change.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/sysbio/syt051DOI Listing
November 2013

Mitochondrial phylogenomics of modern and ancient equids.

PLoS One 2013 20;8(2):e55950. Epub 2013 Feb 20.

Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Copenhagen, Denmark.

The genus Equus is richly represented in the fossil record, yet our understanding of taxonomic relationships within this genus remains limited. To estimate the phylogenetic relationships among modern horses, zebras, asses and donkeys, we generated the first data set including complete mitochondrial sequences from all seven extant lineages within the genus Equus. Bayesian and Maximum Likelihood phylogenetic inference confirms that zebras are monophyletic within the genus, and the Plains and Grevy's zebras form a well-supported monophyletic group. Using ancient DNA techniques, we further characterize the complete mitochondrial genomes of three extinct equid lineages (the New World stilt-legged horses, NWSLH; the subgenus Sussemionus; and the Quagga, Equus quagga quagga). Comparisons with extant taxa confirm the NWSLH as being part of the caballines, and the Quagga and Plains zebras as being conspecific. However, the evolutionary relationships among the non-caballine lineages, including the now-extinct subgenus Sussemionus, remain unresolved, most likely due to extremely rapid radiation within this group. The closest living outgroups (rhinos and tapirs) were found to be too phylogenetically distant to calibrate reliable molecular clocks. Additional mitochondrial genome sequence data, including radiocarbon dated ancient equids, will be required before revisiting the exact timing of the lineage radiation leading up to modern equids, which for now were found to have possibly shared a common ancestor as far as up to 4 Million years ago (Mya).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0055950PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3577844PMC
August 2013

Genomic diversity and evolution of the head crest in the rock pigeon.

Science 2013 Mar 31;339(6123):1063-7. Epub 2013 Jan 31.

Department of Biology, University of Utah, Salt Lake City, UT 84112, USA.

The geographic origins of breeds and the genetic basis of variation within the widely distributed and phenotypically diverse domestic rock pigeon (Columba livia) remain largely unknown. We generated a rock pigeon reference genome and additional genome sequences representing domestic and feral populations. We found evidence for the origins of major breed groups in the Middle East and contributions from a racing breed to North American feral populations. We identified the gene EphB2 as a strong candidate for the derived head crest phenotype shared by numerous breeds, an important trait in mate selection in many avian species. We also found evidence that this trait evolved just once and spread throughout the species, and that the crest originates early in development by the localized molecular reversal of feather bud polarity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1126/science.1230422DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3778192PMC
March 2013