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

Publication ,  Journal Article
Bricault, CA; Yusim, K; Seaman, MS; Yoon, H; Theiler, J; Giorgi, EE; Wagh, K; Theiler, M; Hraber, P; Macke, JP; Kreider, EF; Learn, GH ...
Published in: Cell Host Microbe
January 9, 2019

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.

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Published In

Cell Host Microbe

DOI

EISSN

1934-6069

Publication Date

January 9, 2019

Volume

25

Issue

1

Start / End Page

59 / 72.e8

Location

United States

Related Subject Headings

  • env Gene Products, Human Immunodeficiency Virus
  • Vaccines
  • Vaccination
  • Protein Binding
  • Peptide Fragments
  • Mutation
  • Models, Molecular
  • Inhibitory Concentration 50
  • Immunology
  • Immunization
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Bricault, C. A., Yusim, K., Seaman, M. S., Yoon, H., Theiler, J., Giorgi, E. E., … Korber, B. (2019). HIV-1 Neutralizing Antibody Signatures and Application to Epitope-Targeted Vaccine Design. Cell Host Microbe, 25(1), 59-72.e8. https://doi.org/10.1016/j.chom.2018.12.001
Bricault, Christine A., Karina Yusim, Michael S. Seaman, Hyejin Yoon, James Theiler, Elena E. Giorgi, Kshitij Wagh, et al. “HIV-1 Neutralizing Antibody Signatures and Application to Epitope-Targeted Vaccine Design.Cell Host Microbe 25, no. 1 (January 9, 2019): 59-72.e8. https://doi.org/10.1016/j.chom.2018.12.001.
Bricault CA, Yusim K, Seaman MS, Yoon H, Theiler J, Giorgi EE, et al. HIV-1 Neutralizing Antibody Signatures and Application to Epitope-Targeted Vaccine Design. Cell Host Microbe. 2019 Jan 9;25(1):59-72.e8.
Bricault, Christine A., et al. “HIV-1 Neutralizing Antibody Signatures and Application to Epitope-Targeted Vaccine Design.Cell Host Microbe, vol. 25, no. 1, Jan. 2019, pp. 59-72.e8. Pubmed, doi:10.1016/j.chom.2018.12.001.
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. HIV-1 Neutralizing Antibody Signatures and Application to Epitope-Targeted Vaccine Design. Cell Host Microbe. 2019 Jan 9;25(1):59-72.e8.
Journal cover image

Published In

Cell Host Microbe

DOI

EISSN

1934-6069

Publication Date

January 9, 2019

Volume

25

Issue

1

Start / End Page

59 / 72.e8

Location

United States

Related Subject Headings

  • env Gene Products, Human Immunodeficiency Virus
  • Vaccines
  • Vaccination
  • Protein Binding
  • Peptide Fragments
  • Mutation
  • Models, Molecular
  • Inhibitory Concentration 50
  • Immunology
  • Immunization