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


ABSTRACT: 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.

SUBMITTER: Zhou T 

PROVIDER: S-EPMC5538809 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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

Zhou Tongqing T   Doria-Rose Nicole A NA   Cheng Cheng C   Stewart-Jones Guillaume B E GBE   Chuang Gwo-Yu GY   Chambers Michael M   Druz Aliaksandr A   Geng Hui H   McKee Krisha K   Kwon Young Do YD   O'Dell Sijy S   Sastry Mallika M   Schmidt Stephen D SD   Xu Kai K   Chen Lei L   Chen Rita E RE   Louder Mark K MK   Pancera Marie M   Wanninger Timothy G TG   Zhang Baoshan B   Zheng Anqi A   Farney S Katie SK   Foulds Kathryn E KE   Georgiev Ivelin S IS   Joyce M Gordon MG   Lemmin Thomas T   Narpala Sandeep S   Rawi Reda R   Soto Cinque C   Todd John-Paul JP   Shen Chen-Hsiang CH   Tsybovsky Yaroslav Y   Yang Yongping Y   Zhao Peng P   Haynes Barton F BF   Stamatatos Leonidas L   Tiemeyer Michael M   Wells Lance L   Scorpio Diana G DG   Shapiro Lawrence L   McDermott Adrian B AB   Mascola John R JR   Kwong Peter D PD  

Cell reports 20170401 4


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 yield  ...[more]

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