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- Rose Mathew, Nimitha, 1987, et al.
(författare)
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Recombinant Influenza Vaccines: Saviors to Overcome Immunodominance
- 2020
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Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 10
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Forskningsöversikt (refereegranskat)abstract
- It has been almost a decade since the 2009 influenza A virus pandemic hit the globe causing significant morbidity and mortality. Nonetheless, annual influenza vaccination, which elicits antibodies mainly against the head region of influenza hemagglutinin (HA), remains as the mainstay to combat and reduce symptoms of influenza infection. Influenza HA is highly antigenically variable, thus limiting vaccine efficacy. In addition, the variable HA head occupies the upper strata of the immunodominance hierarchy, thereby clouding the antibody response toward subdominant epitopes, which are usually conserved across different influenza strains. Isolation of monoclonal antibodies from individuals recognizing such epitopes has facilitated the development of recombinant vaccines that focus the adaptive immune response toward conserved, protective targets. Here, we review some significant leaps in recombinant vaccine development, which could possibly help to overcome B cell and antibody immunodominance and provide heterosubtypic immunity to influenza A virus.
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| 2. |
- Rose Mathew, Nimitha, 1987, et al.
(författare)
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Single-cell BCR and transcriptome analysis after influenza infection reveals spatiotemporal dynamics of antigen-specific B cells
- 2021
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Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 35:12
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Tidskriftsartikel (refereegranskat)abstract
- B cell responses are critical for antiviral immunity. However, a comprehensive picture of antigen-specific B cell differentiation, clonal proliferation, and dynamics in different organs after infection is lacking. Here, by combining single-cell RNA and B cell receptor (BCR) sequencing of antigen-specific cells in lymph nodes, spleen, and lungs after influenza infection in mice, we identify several germinal center (GC) B cell subpopulations and organ-specific differences that persist over the course of the response. We discover transcriptional differences between memory cells in lungs and lymphoid organs and organ-restricted clonal expansion. Remarkably, we find significant clonal overlap between GC-derived memory and plasma cells. By combining BCR-mutational analyses with monoclonal antibody (mAb) expression and affinity measurements, we find that memory B cells are highly diverse and can be selected from both low- and high-affinity precursors. By linking antigen recognition with transcriptional programming, clonal proliferation, and differentiation, these finding provide important advances in our understanding of antiviral immunity.
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| 3. |
- Scharf, Lydia, et al.
(författare)
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Longitudinal single-cell analysis of SARS-CoV-2-reactive B cells uncovers persistence of early-formed, antigen specific clones.
- 2023
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Ingår i: JCI insight. - : American Society for Clinical Investigation. - 2379-3708. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Understanding persistence and evolution of B cell clones after COVID-19 infection and vaccination is crucial for predicting responses against emerging viral variants and optimizing vaccines. Here, we collected longitudinal samples from severe COVID-19 patients every third to seventh day during hospitalization and every third month after recovery. We profiled the antigen-specific immune cell dynamics by combining single cell RNA-Seq, Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE)-Seq, B cell receptor (BCR)-Seq with oligo-tagged antigen baits. While the proportion of Spike Receptor Binding Domain-specific memory B cells (MBC) increased from 3 months after infection, the other Spike- and Nucleocapsid-specific B cells remained constant. All patients showed ongoing class switching and sustained affinity maturation of antigen specific cells, which was not significantly increased early after vaccine. B cell analysis revealed a polyclonal response with limited clonal expansion; nevertheless, some clones detected during hospitalization, as plasmablasts, persisted for up to one year, as MBC. Monoclonal antibodies derived from persistent B cell families increased their binding and neutralization breadth and started recognizing viral variants by 3 months after infection. Overall, our findings provide important insights into the clonal evolution and dynamics of antigen specific B cell responses in longitudinally sampled COVID-19 infected patients.
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