CD4 T cell epitope abundance in ferritin core potentiates responses to hemagglutinin nanoparticle vaccines
Abstract Nanoparticle vaccines based on H. pylori ferritin are increasingly used as a vaccine platform for many pathogens, including RSV, influenza, and SARS-CoV-2. They have been found to elicit enhanced, long-lived B cell responses. The basis for improved efficacy of ferritin nanoparticle vaccines...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-10-01
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| Series: | npj Vaccines |
| Online Access: | https://doi.org/10.1038/s41541-022-00547-0 |
| _version_ | 1797641998501412864 |
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| author | Sean A. Nelson Katherine A. Richards Maryah A. Glover Francisco A. Chaves Michelle C. Crank Barney S. Graham Masaru Kanekiyo Andrea J. Sant |
| author_facet | Sean A. Nelson Katherine A. Richards Maryah A. Glover Francisco A. Chaves Michelle C. Crank Barney S. Graham Masaru Kanekiyo Andrea J. Sant |
| author_sort | Sean A. Nelson |
| collection | DOAJ |
| description | Abstract Nanoparticle vaccines based on H. pylori ferritin are increasingly used as a vaccine platform for many pathogens, including RSV, influenza, and SARS-CoV-2. They have been found to elicit enhanced, long-lived B cell responses. The basis for improved efficacy of ferritin nanoparticle vaccines remains unresolved, including whether recruitment of CD4 T cells specific for the ferritin component of these vaccines contributes to cognate help in the B cell response. Using influenza HA-ferritin nanoparticles as a prototype, we have performed an unbiased assessment of the CD4 T cell epitope composition of the ferritin particles relative to that contributed by influenza HA using mouse models that express distinct constellations of MHC class II molecules. The role that these CD4 T cells play in the B cell responses was assessed by quantifying follicular helper cells (TFH), germinal center (GC) B cells, and antibody secreting cells. When mice were immunized with equimolar quantities of soluble HA-trimers and HA-Fe nanoparticles, HA-nanoparticle immunized mice had an increased overall abundance of TFH that were found to be largely ferritin-specific. HA-nanoparticle immunized mice had an increased abundance of HA-specific isotype-switched GC B cells and HA-specific antibody secreting cells (ASCs) relative to mice immunized with soluble HA-trimers. Further, there was a strong, positive correlation between CD4 TFH abundance and GC B cell abundance. Thus, availability of helper CD4 T cell epitopes may be a key additional mechanism that underlies the enhanced immunogenicity of ferritin-based HA-Fe-nanoparticle vaccines. |
| first_indexed | 2024-03-11T13:53:50Z |
| format | Article |
| id | doaj.art-fdb8daa72b4e4c18aca6e6142b4badea |
| institution | Directory Open Access Journal |
| issn | 2059-0105 |
| language | English |
| last_indexed | 2024-03-11T13:53:50Z |
| publishDate | 2022-10-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Vaccines |
| spelling | doaj.art-fdb8daa72b4e4c18aca6e6142b4badea2023-11-02T07:52:59ZengNature Portfolionpj Vaccines2059-01052022-10-017111310.1038/s41541-022-00547-0CD4 T cell epitope abundance in ferritin core potentiates responses to hemagglutinin nanoparticle vaccinesSean A. Nelson0Katherine A. Richards1Maryah A. Glover2Francisco A. Chaves3Michelle C. Crank4Barney S. Graham5Masaru Kanekiyo6Andrea J. Sant7David H. Smith Center for Vaccine Biology and Immunology, Department of Microbiology and Immunology, University of Rochester Medical CenterDavid H. Smith Center for Vaccine Biology and Immunology, Department of Microbiology and Immunology, University of Rochester Medical CenterDavid H. Smith Center for Vaccine Biology and Immunology, Department of Microbiology and Immunology, University of Rochester Medical CenterDavid H. Smith Center for Vaccine Biology and Immunology, Department of Microbiology and Immunology, University of Rochester Medical CenterVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of HealthVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of HealthVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of HealthDavid H. Smith Center for Vaccine Biology and Immunology, Department of Microbiology and Immunology, University of Rochester Medical CenterAbstract Nanoparticle vaccines based on H. pylori ferritin are increasingly used as a vaccine platform for many pathogens, including RSV, influenza, and SARS-CoV-2. They have been found to elicit enhanced, long-lived B cell responses. The basis for improved efficacy of ferritin nanoparticle vaccines remains unresolved, including whether recruitment of CD4 T cells specific for the ferritin component of these vaccines contributes to cognate help in the B cell response. Using influenza HA-ferritin nanoparticles as a prototype, we have performed an unbiased assessment of the CD4 T cell epitope composition of the ferritin particles relative to that contributed by influenza HA using mouse models that express distinct constellations of MHC class II molecules. The role that these CD4 T cells play in the B cell responses was assessed by quantifying follicular helper cells (TFH), germinal center (GC) B cells, and antibody secreting cells. When mice were immunized with equimolar quantities of soluble HA-trimers and HA-Fe nanoparticles, HA-nanoparticle immunized mice had an increased overall abundance of TFH that were found to be largely ferritin-specific. HA-nanoparticle immunized mice had an increased abundance of HA-specific isotype-switched GC B cells and HA-specific antibody secreting cells (ASCs) relative to mice immunized with soluble HA-trimers. Further, there was a strong, positive correlation between CD4 TFH abundance and GC B cell abundance. Thus, availability of helper CD4 T cell epitopes may be a key additional mechanism that underlies the enhanced immunogenicity of ferritin-based HA-Fe-nanoparticle vaccines.https://doi.org/10.1038/s41541-022-00547-0 |
| spellingShingle | Sean A. Nelson Katherine A. Richards Maryah A. Glover Francisco A. Chaves Michelle C. Crank Barney S. Graham Masaru Kanekiyo Andrea J. Sant CD4 T cell epitope abundance in ferritin core potentiates responses to hemagglutinin nanoparticle vaccines npj Vaccines |
| title | CD4 T cell epitope abundance in ferritin core potentiates responses to hemagglutinin nanoparticle vaccines |
| title_full | CD4 T cell epitope abundance in ferritin core potentiates responses to hemagglutinin nanoparticle vaccines |
| title_fullStr | CD4 T cell epitope abundance in ferritin core potentiates responses to hemagglutinin nanoparticle vaccines |
| title_full_unstemmed | CD4 T cell epitope abundance in ferritin core potentiates responses to hemagglutinin nanoparticle vaccines |
| title_short | CD4 T cell epitope abundance in ferritin core potentiates responses to hemagglutinin nanoparticle vaccines |
| title_sort | cd4 t cell epitope abundance in ferritin core potentiates responses to hemagglutinin nanoparticle vaccines |
| url | https://doi.org/10.1038/s41541-022-00547-0 |
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