Cell Reports (Apr 2021)
Enhancing glycan occupancy of soluble HIV-1 envelope trimers to mimic the native viral spike
- Ronald Derking,
- Joel D. Allen,
- Christopher A. Cottrell,
- Kwinten Sliepen,
- Gemma E. Seabright,
- Wen-Hsin Lee,
- Yoann Aldon,
- Kimmo Rantalainen,
- Aleksandar Antanasijevic,
- Jeffrey Copps,
- Anila Yasmeen,
- Albert Cupo,
- Victor M. Cruz Portillo,
- Meliawati Poniman,
- Niki Bol,
- Patricia van der Woude,
- Steven W. de Taeye,
- Tom L.G.M. van den Kerkhof,
- P.J. Klasse,
- Gabriel Ozorowski,
- Marit J. van Gils,
- John P. Moore,
- Andrew B. Ward,
- Max Crispin,
- Rogier W. Sanders
Affiliations
- Ronald Derking
- Department of Medical Microbiology, Amsterdam Infection and Immunity Institute, Amsterdam UMC, University of Amsterdam, Amsterdam 1105 AZ, the Netherlands
- Joel D. Allen
- School of Biological Sciences, University of Southampton, Southampton SO17 1BJ, UK
- Christopher A. Cottrell
- Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
- Kwinten Sliepen
- Department of Medical Microbiology, Amsterdam Infection and Immunity Institute, Amsterdam UMC, University of Amsterdam, Amsterdam 1105 AZ, the Netherlands
- Gemma E. Seabright
- School of Biological Sciences, University of Southampton, Southampton SO17 1BJ, UK; Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK
- Wen-Hsin Lee
- Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
- Yoann Aldon
- Department of Medical Microbiology, Amsterdam Infection and Immunity Institute, Amsterdam UMC, University of Amsterdam, Amsterdam 1105 AZ, the Netherlands
- Kimmo Rantalainen
- Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
- Aleksandar Antanasijevic
- Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
- Jeffrey Copps
- Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
- Anila Yasmeen
- Department of Microbiology and Immunology, Weill Cornell Medical College, Cornell University, New York, NY, USA
- Albert Cupo
- Department of Microbiology and Immunology, Weill Cornell Medical College, Cornell University, New York, NY, USA
- Victor M. Cruz Portillo
- Department of Microbiology and Immunology, Weill Cornell Medical College, Cornell University, New York, NY, USA
- Meliawati Poniman
- Department of Medical Microbiology, Amsterdam Infection and Immunity Institute, Amsterdam UMC, University of Amsterdam, Amsterdam 1105 AZ, the Netherlands
- Niki Bol
- Department of Medical Microbiology, Amsterdam Infection and Immunity Institute, Amsterdam UMC, University of Amsterdam, Amsterdam 1105 AZ, the Netherlands
- Patricia van der Woude
- Department of Medical Microbiology, Amsterdam Infection and Immunity Institute, Amsterdam UMC, University of Amsterdam, Amsterdam 1105 AZ, the Netherlands
- Steven W. de Taeye
- Department of Medical Microbiology, Amsterdam Infection and Immunity Institute, Amsterdam UMC, University of Amsterdam, Amsterdam 1105 AZ, the Netherlands
- Tom L.G.M. van den Kerkhof
- Department of Medical Microbiology, Amsterdam Infection and Immunity Institute, Amsterdam UMC, University of Amsterdam, Amsterdam 1105 AZ, the Netherlands
- P.J. Klasse
- Department of Microbiology and Immunology, Weill Cornell Medical College, Cornell University, New York, NY, USA
- Gabriel Ozorowski
- Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA; Center for HIV/AIDS Vaccine Development, IAVI Neutralizing Antibody Center and the Collaboration for AIDS Vaccine Discovery (CAVD), The Scripps Research Institute, La Jolla, CA 92037, USA
- Marit J. van Gils
- Department of Medical Microbiology, Amsterdam Infection and Immunity Institute, Amsterdam UMC, University of Amsterdam, Amsterdam 1105 AZ, the Netherlands
- John P. Moore
- Department of Microbiology and Immunology, Weill Cornell Medical College, Cornell University, New York, NY, USA
- Andrew B. Ward
- Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA; Center for HIV/AIDS Vaccine Development, IAVI Neutralizing Antibody Center and the Collaboration for AIDS Vaccine Discovery (CAVD), The Scripps Research Institute, La Jolla, CA 92037, USA
- Max Crispin
- School of Biological Sciences, University of Southampton, Southampton SO17 1BJ, UK; Corresponding author
- Rogier W. Sanders
- Department of Medical Microbiology, Amsterdam Infection and Immunity Institute, Amsterdam UMC, University of Amsterdam, Amsterdam 1105 AZ, the Netherlands; Department of Microbiology and Immunology, Weill Cornell Medical College, Cornell University, New York, NY, USA; Corresponding author
- Journal volume & issue
-
Vol. 35,
no. 1
p. 108933
Abstract
Summary: Artificial glycan holes on recombinant Env-based vaccines occur when a potential N-linked glycosylation site (PNGS) is under-occupied, but not on their viral counterparts. Native-like SOSIP trimers, including clinical candidates, contain such holes in the glycan shield that induce strain-specific neutralizing antibodies (NAbs) or non-NAbs. To eliminate glycan holes and mimic the glycosylation of native BG505 Env, we replace all 12 NxS sequons on BG505 SOSIP with NxT. All PNGS, except N133 and N160, are nearly fully occupied. Occupancy of the N133 site is increased by changing N133 to NxS, whereas occupancy of the N160 site is restored by reverting the nearby N156 sequon to NxS. Hence, PNGS in close proximity, such as in the N133-N137 and N156-N160 pairs, affect each other’s occupancy. We further apply this approach to improve the occupancy of several Env strains. Increasing glycan occupancy should reduce off-target immune responses to vaccine antigens.
