We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Aggregation by peptide conjugation rescues poor immunogenicity of the HA stem.
- Authors
Jiang, Wenbo; Pilkington, Emily H.; Kelly, Hannah G.; Tan, Hyon-Xhi; Juno, Jennifer A.; Wheatley, Adam K.; Kent, Stephen J.
- Abstract
Influenza virus infection is a global public health threat. Current seasonal influenza vaccines are efficacious only when vaccine strains are matched with circulating strains. There is a critical need for developing "universal" vaccines that protect against all influenza viruses. HA stem is a promising target for developing broad-spectrum influenza vaccines due to its relatively conserved feature. However, HA stem is weakly immunogenic when administered alone in a soluble form. Several approaches have been employed to improve the immunogenicity of HA stem, including conjugation of HA stem with a highly immunogenic carrier protein or displaying HA stem on a nanoparticle scaffold. Converting a weakly immunologic protein into a multimer through aggregation can significantly enhance its immunogenicity, with some multimeric protein aggregates previously shown to be more immunogenic than their soluble counterparts in animal models. Here, we show that a chemically coupling a peptide derived from the head domain of PR8 HA (P35) with the poorly immunogenic HA stem protein results in aggregation of the HA stem which significantly increases stem-specific B cell responses following vaccination. Importantly, vaccination with this conjugate in the absence of adjuvant still induced robust B cell responses against stem in vivo. Improving HA stem immunogenicity by aggregation provides an alternative avenue to conjugation with exotic carrier proteins or nanoparticle formulation.
- Subjects
CARRIER proteins; SEASONAL influenza; INFLUENZA vaccines; VIRUS diseases; INFLUENZA A virus
- Publication
PLoS ONE, 2020, Vol 15, Issue 11, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0241649