Outflanking immunodominance to target subdominant broadly neutralizing epitopes Journal Article
| Authors: | Angeletti, D.; Kosik, I.; Santos, J. J. S.; Yewdell, W. T.; Boudreau, C. M.; Mallajosyula, V. V. A.; Mankowski, M. C.; Chambers, M.; Prabhakaran, M.; Hickman, H. D.; McDermott, A. B.; Alter, G.; Chaudhuri, J.; Yewdell, J. W. |
| Article Title: | Outflanking immunodominance to target subdominant broadly neutralizing epitopes |
| 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. |
| Keywords: | antibodies; influenza; b cell; immunodominance; hemagglutinin |
| Journal Title: | Proceedings of the National Academy of Sciences of the United States of America |
| Volume: | 116 |
| Issue: | 27 |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Date Published: | 2019-07-01 |
| Start Page: | 13474 |
| End Page: | 13479 |
| Language: | English |
| DOI: | 10.1073/pnas.1816300116 |
| PUBMED: | 31213541 |
| PROVIDER: | scopus |
| PMCID: | PMC6612916 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
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