B and T Cell Determinants of Influenza Vaccine Responses in the Elderly
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ABSTRACT: The study sequenced antibody heavy chain gene rearrangements from human subjects receiving influenza vaccination.
SECONDARY ACCESSION(S): PRJNA222239PRJNA222238
REPOSITORIES: dbGaP
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Project description:<p>The study sequenced antibody heavy chain gene rearrangements from 4 identical twin pairs undergoing vaccination with Varicella Zoster viral vaccine.</p>
| phs000817 | dbGaP
Project description:<p>The data consist of the DNA sequences of antibody gene rearrangements from peripheral blood human B cells of subjects vaccinated with trivalent seasonal influenza or monovalent pandemic H1N1 vaccine. Multiple replicate libraries of immunoglobulin heavy chain gene rearrangements were prepared from each subject for each time point.</p>
| phs000760 | dbGaP
Project description:<p>We developed an improved high throughput sequencing approach to measure the quantities and sequences of the repertoire of antibody heavy chain RNA in a blood sample. Using this approach we analyzed the antibody repertoire in response to yearly vaccinations with influenza vaccines TIV and LAIV in healthy adults in two subsequent years. We determined vaccine response patterns specific to LAIV and TIV and found antibody sequences that were shared between two samples of the same individuals following influenza vaccination in subsequent years, thereby providing a genetic measurement of B-cell memory recall.</p>
| phs000656 | dbGaP
Project description:<p>We developed an improved high throughput sequencing approach to measure the quantities and sequences of the repertoire of antibody heavy chain RNA in a blood sample. Using this approach we analyzed the antibody repertoire in response to yearly vaccinations with influenza vaccines TIV and LAIV in healthy adults in two subsequent years. We determined vaccine response patterns specific to LAIV and TIV and found antibody sequences that were shared between two samples of the same individuals following influenza vaccination in subsequent years, thereby providing a genetic measurement of B-cell memory recall.</p>
| phs000656.v1.p1 | EGA
Project description:Influenza virus vaccination remains the best strategy for combating virus infection, but vaccine efficacy is highly variable. An ideal influenza vaccine must have two attributes: one, it should be capable of inducing broadly cross-reactive antibodies that can neutralize diverse influenza virus strains; and two, it must induce long-lived antibody responses to maintain protective immunity for extended periods. Germinal center (GC) reactions are the major sites where diversification and affinity maturation of B cells occur. Whether a persistent GC response could expand the breadth of responding B cell clones following influenza vaccination in humans remains unknown. Here, we show that influenza virus vaccine-specific GC B cells persist for over nine weeks post vaccination in two out of seven individuals. These late vaccine-specific GC B cells exhibited increased somatic hypermutation (SHM) of their B cell receptors compared to early vaccine-specific GC B cells. After re-immunization with seasonal influenza virus vaccine, individuals with a persistent GC engaged vaccine-specific plasmablasts (PBs) with higher SHM frequency. Tracking the maturation of three clonally related GC B cell lineages over time revealed that late GC B cells had receptors that recognized and neutralized heterologous influenza virus strains. Thus, SHM induced by persistent GCs can broaden the antibody response to influenza virus vaccination. This indicates that seasonal influenza virus vaccination in humans can induce broadly cross-reactive antibodies that target diverse influenza virus strains.
2024-06-13 | GSE211865 | GEO
Project description:Influenza virus vaccination remains the best strategy for combating virus infection, but vaccine efficacy is highly variable. An ideal influenza vaccine must have two attributes: one, it should be capable of inducing broadly cross-reactive antibodies that can neutralize diverse influenza virus strains; and two, it must induce long-lived antibody responses to maintain protective immunity for extended periods. Germinal center (GC) reactions are the major sites where diversification and affinity maturation of B cells occur. Whether a persistent GC response could expand the breadth of responding B cell clones following influenza vaccination in humans remains unknown. Here, we show that influenza virus vaccine-specific GC B cells persist for over nine weeks post vaccination in two out of seven individuals. These late vaccine-specific GC B cells exhibited increased somatic hypermutation (SHM) of their B cell receptors compared to early vaccine-specific GC B cells. After re-immunization with seasonal influenza virus vaccine, individuals with a persistent GC engaged vaccine-specific plasmablasts (PBs) with higher SHM frequency. Tracking the maturation of three clonally related GC B cell lineages over time revealed that late GC B cells had receptors that recognized and neutralized heterologous influenza virus strains. Thus, SHM induced by persistent GCs can broaden the antibody response to influenza virus vaccination. This indicates that seasonal influenza virus vaccination in humans can induce broadly cross-reactive antibodies that target diverse influenza virus strains.
2024-06-13 | GSE211869 | GEO
Project description:Analysis of the gene expression profiles of naïve B cells, resting memory B cells (MBCs), activated B cells (ABCs) and antibody-secreting cells (ASCs) isolated from peripheral blood one week following influenza vaccination. Upon antigen exposure B cells eventually bifurcate into two distinct lineages, plasmablasts and memory B cells. We previously reported that plasmablasts or antibody-secreting cells (ASCs) could be transiently detected in blood shortly after infection or vaccination of humans. Here, we define the phenotype and the transcriptional program of a novel human antigen-specific B cell subset, referred to as activated B cells (ABCs). ABCs do not spontaneously secrete antibodies and possess a unique transcriptional profile that distinguishes them from ASCs and resting memory B cells. Clonal lineages present among day 7 ABCs persisted in blood for up to three months post-influenza immunization indicating that ABCs may be destined to join the long-term memory B cell pool. ABCs and ASCs can be clearly distinguished in blood following influenza and Ebola virus infections. Interrogating ABCs will expand our understanding of the differentiation, maturation and longevity of human B cell responses. Total RNA was isolated from 10,000 cells of each population.
2015-12-31 | E-GEOD-68245 | biostudies-arrayexpress
Project description:Analysis of the gene expression profiles of naïve B cells, resting memory B cells (MBCs), activated B cells (ABCs) and antibody-secreting cells (ASCs) isolated from peripheral blood one week following influenza vaccination. Upon antigen exposure B cells eventually bifurcate into two distinct lineages, plasmablasts and memory B cells. We previously reported that plasmablasts or antibody-secreting cells (ASCs) could be transiently detected in blood shortly after infection or vaccination of humans. Here, we define the phenotype and the transcriptional program of a novel human antigen-specific B cell subset, referred to as activated B cells (ABCs). ABCs do not spontaneously secrete antibodies and possess a unique transcriptional profile that distinguishes them from ASCs and resting memory B cells. Clonal lineages present among day 7 ABCs persisted in blood for up to three months post-influenza immunization indicating that ABCs may be destined to join the long-term memory B cell pool. ABCs and ASCs can be clearly distinguished in blood following influenza and Ebola virus infections. Interrogating ABCs will expand our understanding of the differentiation, maturation and longevity of human B cell responses.
2015-12-31 | GSE68245 | GEO
Project description:To describe vaccine associated changes in the expression of microRNAs 21 days after vaccination in children receiving one of two pandemic influenza (H1N1) vaccines.
2019-07-13 | GSE134227 | GEO
Project description:Throughout life, humans experience repeated exposure to viral antigens through infection and vaccination, resulting in the generation of diverse, and largely unique, antigen specific antibody repertoires. A paramount feature of antibodies that enables their critical contributions in counteracting recurrent and novel pathogens, and consequently fostering their utility as valuable targets for therapeutic and vaccine development, is the exquisite specificity displayed against their target antigens. Yet, there is still limited understanding of the determinants of antibody-antigen specificity, particularly as a function of antibody sequence. In recent years, experimental characterization of antibody repertoires has led to novel insights into fundamental properties of antibody sequences, but has been largely decoupled from at-scale antigen specificity analysis. Here, using the LIBRA-seq technology, we generated a large dataset mapping antibody sequence to antigen specificity for thousands of B cells, by screening the repertoires of a set of healthy individuals against twenty viral antigens representing diverse pathogens of biomedical significance. Analysis uncovered virus specific patterns in variable gene usage, gene pairing, somatic hypermutation, as well as the presence of convergent antiviral signatures across multiple individuals, including the presence of public antibody clonotypes. Notably, our results showed that, for B cell receptors originating from different individuals but leveraging an identical combination of heavy and light chain variable genes, there is a specific CDRH3/CDRL3 identity threshold that defines whether these B cells may share the same antigen specificity. This finding provides a quantifiable measure of the relationship between antibody sequence and antigen specificity and further defines experimentally grounded criteria for defining public antibody clonality. Understanding the fundamental rules of antibody-antigen interactions can lead to transformative new approaches for the development of antibody therapeutics and vaccines against current and emerging viruses.
2024-08-23 | GSE250159 | GEO