iScience (Aug 2023)
Soluble prefusion-closed HIV-envelope trimers with glycan-covered bases
- Adam S. Olia,
- Cheng Cheng,
- Tongqing Zhou,
- Andrea Biju,
- Darcy R. Harris,
- Anita Changela,
- Hongying Duan,
- Vera B. Ivleva,
- Wing-Pui Kong,
- Li Ou,
- Reda Rawi,
- Yaroslav Tsybovsky,
- David J. Van Wazer,
- Angela R. Corrigan,
- Christopher A. Gonelli,
- Myungjin Lee,
- Krisha McKee,
- Sandeep Narpala,
- Sijy O’Dell,
- Danealle K. Parchment,
- Erik-Stephane D. Stancofski,
- Tyler Stephens,
- Ivy Tan,
- I-Ting Teng,
- Shuishu Wang,
- Qing Wei,
- Yongping Yang,
- Zhengrong Yang,
- Baoshan Zhang,
- Jan Novak,
- Matthew B. Renfrow,
- Nicole A. Doria-Rose,
- Richard A. Koup,
- Adrian B. McDermott,
- Jason G. Gall,
- Q. Paula Lei,
- John R. Mascola,
- Peter D. Kwong
Affiliations
- Adam S. Olia
- Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA
- Cheng Cheng
- Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA
- Tongqing Zhou
- Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA
- Andrea Biju
- Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA
- Darcy R. Harris
- Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA
- Anita Changela
- Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA
- Hongying Duan
- Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA
- Vera B. Ivleva
- Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA
- Wing-Pui Kong
- Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA
- Li Ou
- Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA
- Reda Rawi
- Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA
- Yaroslav Tsybovsky
- Electron Microscopy Laboratory, Cancer Research Technology Program, Leidos Biomedical Research, Inc, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA
- David J. Van Wazer
- Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA
- Angela R. Corrigan
- Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA
- Christopher A. Gonelli
- Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA
- Myungjin Lee
- Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA
- Krisha McKee
- Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA
- Sandeep Narpala
- Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA
- Sijy O’Dell
- Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA
- Danealle K. Parchment
- Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA
- Erik-Stephane D. Stancofski
- Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA
- Tyler Stephens
- Electron Microscopy Laboratory, Cancer Research Technology Program, Leidos Biomedical Research, Inc, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA
- Ivy Tan
- Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA
- I-Ting Teng
- Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA
- Shuishu Wang
- Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA
- Qing Wei
- Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, USA
- Yongping Yang
- Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA
- Zhengrong Yang
- Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL, USA
- Baoshan Zhang
- Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA
- Jan Novak
- Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, USA
- Matthew B. Renfrow
- Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL, USA
- Nicole A. Doria-Rose
- Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA
- Richard A. Koup
- Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA
- Adrian B. McDermott
- Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA
- Jason G. Gall
- Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA
- Q. Paula Lei
- Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA
- John R. Mascola
- Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA
- Peter D. Kwong
- Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA; Corresponding author
- Journal volume & issue
-
Vol. 26,
no. 8
p. 107403
Abstract
Summary: Soluble HIV-1-envelope (Env) trimers elicit immune responses that target their solvent-exposed protein bases, the result of removing these trimers from their native membrane-bound context. To assess whether glycosylation could limit these base responses, we introduced sequons encoding potential N-linked glycosylation sites (PNGSs) into base-proximal regions. Expression and antigenic analyses indicated trimers bearing six-introduced PNGSs to have reduced base recognition. Cryo-EM analysis revealed trimers with introduced PNGSs to be prone to disassembly and introduced PNGS to be disordered. Protein-base and glycan-base trimers induced reciprocally symmetric ELISA responses, in which only a small fraction of the antibody response to glycan-base trimers recognized protein-base trimers and vice versa. EM polyclonal epitope mapping revealed glycan-base trimers –even those that were stable biochemically– to elicit antibodies that recognized disassembled trimers. Introduced glycans can thus mask the protein base but their introduction may yield neo-epitopes that dominate the immune response.
