AI Article Synopsis
- Epitope-focused strategies enhance the development of vaccines targeting broadly neutralizing antibodies (bnAbs) for influenza and similar fast-changing viruses, emphasizing the importance of two conserved sites on the influenza hemagglutinin.
- Research indicates that stem-directed bnAbs may be less common due to potential autoreactivity, which could lead to their elimination by the body's self-tolerance mechanisms.
- Findings reveal that most stem bnAbs reacted with autoantigens, suggesting that stem epitopes might closely resemble host epitopes, while head-directed bnAbs showed less propensity for autoreactivity.
Article Abstract
Epitope-focused approaches for selective clonal induction of broadly neutralizing antibodies (bnAbs) inform most current vaccine strategies for influenza virus and other rapidly evolving pathogens. The two conserved epitopes on the influenza hemagglutinin (HA) - the "stem" and the receptor-binding site (RBS) on the "head" - are the focus of the current "universal" influenza vaccine development efforts. Because stem-directed serum bnAbs are much less abundant than head-directed ones, we hypothesized that the HA stem bnAbs may be autoreactive and thus eliminated through the mechanisms of self-tolerance. We compared autoreactivity profiles of a set of stem and head-directed bnAbs. Most of the stem bnAbs we examined bound autoantigens; several showed staining of HEp-2 cells. A smaller proportion of the head-directed bnAbs were polyreactive. Gene usage did not correlate with autoreactivity. We suggest that complex foreign antigens may often have surface patches resembling some host epitope; our results indicate that HA stem epitopes resemble a host epitope more frequently than does the RBS.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6401307 | PMC |
| http://dx.doi.org/10.1038/s41598-019-40175-8 | DOI Listing |
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