Responses to Varicella Zoster Virus Vaccination
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ABSTRACT: The study sequenced antibody heavy chain gene rearrangements from 4 identical twin pairs undergoing vaccination with Varicella Zoster viral vaccine.
SECONDARY ACCESSION(S): PRJNA264131PRJNA264130
REPOSITORIES: dbGaP
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Project description:<p>The study sequenced antibody heavy chain gene rearrangements from human subjects receiving influenza vaccination.</p>
| phs000666 | 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>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: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
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 | GSE211869 | 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 | GSE211865 | GEO
Project description:The COVID-19 pandemic has generated intense interest in the rapid development and evaluation of vaccine candidates for this disease and other emerging diseases. Several novel methods for preparing vaccine candidates are currently undergoing clinical evaluation in response to the urgent need to prevent the spread of COVID-19. In many cases, these methods rely on new approaches for vaccine production and immune stimulation. We report on the use of a novel method (SolaVAXTM) for production of an inactivated vaccine candidate and the testing of that candidate in a hamster animal model for its ability to prevent infection upon challenge with SARS-CoV-2 virus. The studies employed in this work included an evaluation of the levels of neutralizing antibody produced post-vaccination, levels of specific antibody sub-types to RBD and spike protein that were generated, evaluation of viral shedding post-challenge, flow cytometric and single cell sequencing data on cellular fractions and histopathological evaluation of tissues post-challenge. The results from this study provide insight into the immunological responses occurring as a result of vaccination with the proposed vaccine candidate and the impact that adjuvant formulations, specifically developed to promote Th1 type immune responses, have on vaccine efficacy and protection against infection following challenge with live SARS-CoV-2. This data may have utility in the development of effective vaccine candidates broadly. Furthermore, the results suggest that preparation of a whole virion vaccine for COVID-19 using this specific photochemical method may have utility in the preparation of one such vaccine candidate.
2021-02-19 | GSE165190 | GEO
Project description:Mus musculus antibody heavy chain genes
| PRJNA234768 | ENA
Project description:Paired antibody heavy-light chain sequencing
| PRJEB25901 | ENA