HIV-1 Neutralizing Antibody Signatures and Application to Epitope-Targeted Vaccine Design.

Published

Journal Article

Eliciting HIV-1-specific broadly neutralizing antibodies (bNAbs) remains a challenge for vaccine development, and the potential of passively delivered bNAbs for prophylaxis and therapeutics is being explored. We used neutralization data from four large virus panels to comprehensively map viral signatures associated with bNAb sensitivity, including amino acids, hypervariable region characteristics, and clade effects across four different classes of bNAbs. The bNAb signatures defined for the variable loop 2 (V2) epitope region of HIV-1 Env were then employed to inform immunogen design in a proof-of-concept exploration of signature-based epitope targeted (SET) vaccines. V2 bNAb signature-guided mutations were introduced into Env 459C to create a trivalent vaccine, and immunization of guinea pigs with V2-SET vaccines resulted in increased breadth of NAb responses compared with Env 459C alone. These data demonstrate that bNAb signatures can be utilized to engineer HIV-1 Env vaccine immunogens capable of eliciting antibody responses with greater neutralization breadth.

Full Text

Duke Authors

Cited Authors

  • Bricault, CA; Yusim, K; Seaman, MS; Yoon, H; Theiler, J; Giorgi, EE; Wagh, K; Theiler, M; Hraber, P; Macke, JP; Kreider, EF; Learn, GH; Hahn, BH; Scheid, JF; Kovacs, JM; Shields, JL; Lavine, CL; Ghantous, F; Rist, M; Bayne, MG; Neubauer, GH; McMahan, K; Peng, H; Chéneau, C; Jones, JJ; Zeng, J; Ochsenbauer, C; Nkolola, JP; Stephenson, KE; Chen, B; Gnanakaran, S; Bonsignori, M; Williams, LD; Haynes, BF; Doria-Rose, N; Mascola, JR; Montefiori, DC; Barouch, DH; Korber, B

Published Date

  • January 9, 2019

Published In

Volume / Issue

  • 25 / 1

Start / End Page

  • 59 - 72.e8

PubMed ID

  • 30629920

Pubmed Central ID

  • 30629920

Electronic International Standard Serial Number (EISSN)

  • 1934-6069

Digital Object Identifier (DOI)

  • 10.1016/j.chom.2018.12.001

Language

  • eng

Conference Location

  • United States