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Quantification of the Impact of the HIV-1-Glycan Shield on Antibody Elicitation.

Publication ,  Journal Article
Zhou, T; Doria-Rose, NA; Cheng, C; Stewart-Jones, GBE; Chuang, G-Y; Chambers, M; Druz, A; Geng, H; McKee, K; Kwon, YD; O'Dell, S; Sastry, M ...
Published in: Cell Rep
April 25, 2017

While the HIV-1-glycan shield is known to shelter Env from the humoral immune response, its quantitative impact on antibody elicitation has been unclear. Here, we use targeted deglycosylation to measure the impact of the glycan shield on elicitation of antibodies against the CD4 supersite. We engineered diverse Env trimers with select glycans removed proximal to the CD4 supersite, characterized their structures and glycosylation, and immunized guinea pigs and rhesus macaques. Immunizations yielded little neutralization against wild-type viruses but potent CD4-supersite neutralization (titers 1: >1,000,000 against four-glycan-deleted autologous viruses with over 90% breadth against four-glycan-deleted heterologous strains exhibiting tier 2 neutralization character). To a first approximation, the immunogenicity of the glycan-shielded protein surface was negligible, with Env-elicited neutralization (ID50) proportional to the exponential of the protein-surface area accessible to antibody. Based on these high titers and exponential relationship, we propose site-selective deglycosylated trimers as priming immunogens to increase the frequency of site-targeting antibodies.

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Published In

Cell Rep

DOI

EISSN

2211-1247

Publication Date

April 25, 2017

Volume

19

Issue

4

Start / End Page

719 / 732

Location

United States

Related Subject Headings

  • env Gene Products, Human Immunodeficiency Virus
  • Protein Structure, Quaternary
  • Polysaccharides
  • Molecular Dynamics Simulation
  • Macaca mulatta
  • Immunization
  • Humans
  • HIV-1
  • HIV Antibodies
  • Guinea Pigs
 

Citation

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Zhou, T., Doria-Rose, N. A., Cheng, C., Stewart-Jones, G. B. E., Chuang, G.-Y., Chambers, M., … Kwong, P. D. (2017). Quantification of the Impact of the HIV-1-Glycan Shield on Antibody Elicitation. Cell Rep, 19(4), 719–732. https://doi.org/10.1016/j.celrep.2017.04.013
Zhou, Tongqing, Nicole A. Doria-Rose, Cheng Cheng, Guillaume B. E. Stewart-Jones, Gwo-Yu Chuang, Michael Chambers, Aliaksandr Druz, et al. “Quantification of the Impact of the HIV-1-Glycan Shield on Antibody Elicitation.Cell Rep 19, no. 4 (April 25, 2017): 719–32. https://doi.org/10.1016/j.celrep.2017.04.013.
Zhou T, Doria-Rose NA, Cheng C, Stewart-Jones GBE, Chuang G-Y, Chambers M, et al. Quantification of the Impact of the HIV-1-Glycan Shield on Antibody Elicitation. Cell Rep. 2017 Apr 25;19(4):719–32.
Zhou, Tongqing, et al. “Quantification of the Impact of the HIV-1-Glycan Shield on Antibody Elicitation.Cell Rep, vol. 19, no. 4, Apr. 2017, pp. 719–32. Pubmed, doi:10.1016/j.celrep.2017.04.013.
Zhou T, Doria-Rose NA, Cheng C, Stewart-Jones GBE, Chuang G-Y, Chambers M, Druz A, Geng H, McKee K, Kwon YD, O’Dell S, Sastry M, Schmidt SD, Xu K, Chen L, Chen RE, Louder MK, Pancera M, Wanninger TG, Zhang B, Zheng A, Farney SK, Foulds KE, Georgiev IS, Joyce MG, Lemmin T, Narpala S, Rawi R, Soto C, Todd J-P, Shen C-H, Tsybovsky Y, Yang Y, Zhao P, Haynes BF, Stamatatos L, Tiemeyer M, Wells L, Scorpio DG, Shapiro L, McDermott AB, Mascola JR, Kwong PD. Quantification of the Impact of the HIV-1-Glycan Shield on Antibody Elicitation. Cell Rep. 2017 Apr 25;19(4):719–732.
Journal cover image

Published In

Cell Rep

DOI

EISSN

2211-1247

Publication Date

April 25, 2017

Volume

19

Issue

4

Start / End Page

719 / 732

Location

United States

Related Subject Headings

  • env Gene Products, Human Immunodeficiency Virus
  • Protein Structure, Quaternary
  • Polysaccharides
  • Molecular Dynamics Simulation
  • Macaca mulatta
  • Immunization
  • Humans
  • HIV-1
  • HIV Antibodies
  • Guinea Pigs