Mechanisms that promote the evolution of cross-reactive antibodies upon vaccination with designed influenza immunogens
Summary: Immunogens that elicit broadly neutralizing antibodies targeting the conserved receptor-binding site (RBS) on influenza hemagglutinin may serve as candidates for a universal influenza vaccine. Here, we develop a computational model to interrogate antibody evolution by affinity maturation af...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-03-01
|
| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124723001717 |
| _version_ | 1811160889372442624 |
|---|---|
| author | Leerang Yang Timothy M. Caradonna Aaron G. Schmidt Arup K. Chakraborty |
| author_facet | Leerang Yang Timothy M. Caradonna Aaron G. Schmidt Arup K. Chakraborty |
| author_sort | Leerang Yang |
| collection | DOAJ |
| description | Summary: Immunogens that elicit broadly neutralizing antibodies targeting the conserved receptor-binding site (RBS) on influenza hemagglutinin may serve as candidates for a universal influenza vaccine. Here, we develop a computational model to interrogate antibody evolution by affinity maturation after immunization with two types of immunogens: a heterotrimeric “chimera” hemagglutinin that is enriched for the RBS epitope relative to other B cell epitopes and a cocktail composed of three non-epitope-enriched homotrimers of the monomers that comprise the chimera. Experiments in mice find that the chimera outperforms the cocktail for eliciting RBS-directed antibodies. We show that this result follows from an interplay between how B cells engage these antigens and interact with diverse helper T cells and requires T cell-mediated selection of germinal center B cells to be a stringent constraint. Our results shed light on antibody evolution and highlight how immunogen design and T cells modulate vaccination outcomes. |
| first_indexed | 2024-04-10T06:04:57Z |
| format | Article |
| id | doaj.art-aea04b021c99479da415842e9e2c2aa2 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-04-10T06:04:57Z |
| publishDate | 2023-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-aea04b021c99479da415842e9e2c2aa22023-03-03T04:24:27ZengElsevierCell Reports2211-12472023-03-01423112160Mechanisms that promote the evolution of cross-reactive antibodies upon vaccination with designed influenza immunogensLeerang Yang0Timothy M. Caradonna1Aaron G. Schmidt2Arup K. Chakraborty3Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USARagon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USARagon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; Department of Microbiology, Harvard Medical School, Boston, MA 02115, USADepartment of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; Department of Physics, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Institute of Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Corresponding authorSummary: Immunogens that elicit broadly neutralizing antibodies targeting the conserved receptor-binding site (RBS) on influenza hemagglutinin may serve as candidates for a universal influenza vaccine. Here, we develop a computational model to interrogate antibody evolution by affinity maturation after immunization with two types of immunogens: a heterotrimeric “chimera” hemagglutinin that is enriched for the RBS epitope relative to other B cell epitopes and a cocktail composed of three non-epitope-enriched homotrimers of the monomers that comprise the chimera. Experiments in mice find that the chimera outperforms the cocktail for eliciting RBS-directed antibodies. We show that this result follows from an interplay between how B cells engage these antigens and interact with diverse helper T cells and requires T cell-mediated selection of germinal center B cells to be a stringent constraint. Our results shed light on antibody evolution and highlight how immunogen design and T cells modulate vaccination outcomes.http://www.sciencedirect.com/science/article/pii/S2211124723001717CP: Immunology |
| spellingShingle | Leerang Yang Timothy M. Caradonna Aaron G. Schmidt Arup K. Chakraborty Mechanisms that promote the evolution of cross-reactive antibodies upon vaccination with designed influenza immunogens Cell Reports CP: Immunology |
| title | Mechanisms that promote the evolution of cross-reactive antibodies upon vaccination with designed influenza immunogens |
| title_full | Mechanisms that promote the evolution of cross-reactive antibodies upon vaccination with designed influenza immunogens |
| title_fullStr | Mechanisms that promote the evolution of cross-reactive antibodies upon vaccination with designed influenza immunogens |
| title_full_unstemmed | Mechanisms that promote the evolution of cross-reactive antibodies upon vaccination with designed influenza immunogens |
| title_short | Mechanisms that promote the evolution of cross-reactive antibodies upon vaccination with designed influenza immunogens |
| title_sort | mechanisms that promote the evolution of cross reactive antibodies upon vaccination with designed influenza immunogens |
| topic | CP: Immunology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124723001717 |
| work_keys_str_mv | AT leerangyang mechanismsthatpromotetheevolutionofcrossreactiveantibodiesuponvaccinationwithdesignedinfluenzaimmunogens AT timothymcaradonna mechanismsthatpromotetheevolutionofcrossreactiveantibodiesuponvaccinationwithdesignedinfluenzaimmunogens AT aarongschmidt mechanismsthatpromotetheevolutionofcrossreactiveantibodiesuponvaccinationwithdesignedinfluenzaimmunogens AT arupkchakraborty mechanismsthatpromotetheevolutionofcrossreactiveantibodiesuponvaccinationwithdesignedinfluenzaimmunogens |