Structure-Guided Molecular Grafting of a Complex Broadly Neutralizing Viral Epitope.

Journal Article (Journal Article)

Antigenic variation and viral evolution have thwarted traditional influenza vaccination strategies. The broad protection afforded by a "universal" influenza vaccine may come from immunogens that elicit humoral immune responses targeting conserved epitopes on the viral hemagglutinin (HA), such as the receptor-binding site (RBS). Here, we engineered candidate immunogens that use noncirculating, avian influenza HAs as molecular scaffolds to present the broadly neutralizing RBS epitope from historical, circulating H1 influenzas. These "resurfaced" HAs (rsHAs) remove epitopes potentially targeted by strain-specific responses in immune-experienced individuals. Through structure-guided optimization, we improved two antigenically different scaffolds to bind a diverse panel of pan-H1 and H1/H3 cross-reactive bnAbs with high affinity. Subsequent serological and single germinal center B cell analyses from murine prime-boost immunizations show that the rsHAs are both immunogenic and can augment the quality of elicited RBS-directed antibodies. Our structure-guided, RBS grafting approach provides candidate immunogens for selectively presenting a conserved viral epitope.

Full Text

Duke Authors

Cited Authors

  • Bajic, G; Maron, MJ; Caradonna, TM; Tian, M; Mermelstein, A; Fera, D; Kelsoe, G; Kuraoka, M; Schmidt, AG

Published Date

  • May 8, 2020

Published In

Volume / Issue

  • 6 / 5

Start / End Page

  • 1182 - 1191

PubMed ID

  • 32267676

Pubmed Central ID

  • PMC7291361

Electronic International Standard Serial Number (EISSN)

  • 2373-8227

Digital Object Identifier (DOI)

  • 10.1021/acsinfecdis.0c00008

Language

  • eng

Conference Location

  • United States