| 1. |
- Angeletti, Davide, 1984, et al.
(författare)
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Outflanking immunodominance to target subdominant broadly neutralizing epitopes
- 2019
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 116:27, s. 13474-13479
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Tidskriftsartikel (refereegranskat)abstract
- A major obstacle to vaccination against antigenically variable viruses is skewing of antibody responses to variable immunodominant epitopes. For influenza virus hemagglutinin (HA), the immunodominance of the variable head impairs responses to the highly conserved stem. Here, we show that head immunodominance depends on the physical attachment of head to stem. Stem immunogenicity is enhanced by immunizing with stem-only constructs or by increasing local HA concentration in the draining lymph node. Surprisingly, coimmunization of full-length HA and stem alters stem-antibody class switching. Our findings delineate strategies for overcoming immunodominance, with important implications for human vaccination. © 2019 National Academy of Sciences. All rights reserved.
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| 2. |
- Yewdell, W. T., et al.
(författare)
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Temporal dynamics of persistent germinal centers and memory B cell differentiation following respiratory virus infection
- 2021
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Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 37:6
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Tidskriftsartikel (refereegranskat)abstract
- Following infection or immunization, memory B cells (MBCs) and long-lived plasma cells provide humoral immunity that can last for decades. Most principles of MBC biology have been determined with hapten-protein carrier models or fluorescent protein immunizations. Here, we examine the temporal dynamics of the germinal center (GC) B cell and MBC response following mouse influenza A virus infection. We find that antiviral B cell responses within the lung-draining mediastinal lymph node (mLN) and the spleen are distinct in regard to duration, enrichment for antigen-binding cells, and class switching dynamics. While splenic GCs dissolve after 6 weeks post-infection, mLN hemagglutinin-specific (HA(+)) GCs can persist for 22 weeks. Persistent GCs continuously differentiate MBCs, with "peak"and "late"GCs contributing equal numbers of HA(+) MBCs to the long-lived compartment. Our findings highlight critical aspects of persistent GC responses and MBC differentiation following respiratory virus infection with direct implications for developing effective vaccination strategies.
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| 3. |
- Clemens, E., et al.
(författare)
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Influenza-infected newborn and adult monkeys exhibit a strong primary antibody response to hemagglutinin stem
- 2020
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Ingår i: Jci Insight. - : American Society for Clinical Investigation. - 2379-3708. ; 5:5
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Tidskriftsartikel (refereegranskat)abstract
- The specificity of antibodies (Abs) generated against influenza A virus (IAV) infection can significantly alter protection and viral clearance. At present, the impact of age upon this process is relatively unexplored. Here, we evaluated the Ab response in newborn and adult African green monkeys following infection with IAV using a strain that enables usto determine the immunodominance (ID) hierarchy of the Ab response to hemagglutinin (HA), the principal target of protective Abs. This revealed altered ID patterns in the early IgM anti-HA response in newborns versus adults that converged over time. While the lgG ID profiles for HA in newborn and adult monkeys were similar, this was not the case for IgA. Importantly, HA stem-specific Abs were generated robustly and similarly in newborns and adults in terms of quality and quantity. Together, these results demonstrate that newborns and adults can differ in the Ab ID pattern established following infection and that the ID pattern can vary across isotypes. In addition, newborns have the ability to generate potent HA stem-specific Ab responses. Our findings further the understanding of the newborn response to IAV antigens and inform the development of improved vaccines for this at-risk population.
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