Closing and Opening Holes in the Glycan Shield of HIV-1 Envelope Glycoprotein SOSIP Trimers Can Redirect the Neutralizing Antibody Response to the Newly Unmasked Epitopes | Zendy

Rajesh P. Ringe | Zendy; Pavel Pugach | Zendy; Christopher A. Cottrell | Zendy; Celia C. LaBranche | Zendy; Gemma E. Seabright | Zendy; Thomas J. Ketas | Zendy; Gabriel Ozorowski | Zendy; Sonu Kumar | Zendy; Anna Schorcht | Zendy; Marit J. van Gils | Zendy; Max Crispin | Zendy; David C. Montefiori | Zendy; Ian A. Wilson | Zendy; Andrew B. Ward | Zendy; Rogier W. Sanders | Zendy; Per Johan Klasse | Zendy; John P. Moore | Zendy

Open Access

Closing and Opening Holes in the Glycan Shield of HIV-1 Envelope Glycoprotein SOSIP Trimers Can Redirect the Neutralizing Antibody Response to the Newly Unmasked Epitopes

Author(s) -

Rajesh P. Ringe,

Pavel Pugach,

Christopher A. Cottrell,

Celia C. LaBranche,

Gemma E. Seabright,

Thomas J. Ketas,

Gabriel Ozorowski,

Sonu Kumar,

Anna Schorcht,

Marit J. van Gils,

Max Crispin,

David C. Montefiori,

Ian A. Wilson,

Andrew B. Ward,

Rogier W. Sanders,

Per Johan Klasse,

John P. Moore

Publication year - 2018

Publication title -

journal of virology

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 2.617

H-Index - 292

eISSN - 1070-6321

pISSN - 0022-538X

DOI - 10.1128/jvi.01656-18

Subject(s) - epitope , glycan , trimer , immunogen , neutralizing antibody , glycobiology , antibody dependent cell mediated cytotoxicity , biology , glycoprotein , epitope mapping , antibody , chemistry , microbiology and biotechnology , virology , immunology , monoclonal antibody , dimer , organic chemistry

Engineered SOSIP trimers mimic envelope-glycoprotein spikes, which stud the surface of HIV-1 particles and mediate viral entry into cells. When used for immunizing test animals, they elicit antibodies that neutralize resistant sequence-matched HIV-1 isolates. These neutralizing antibodies recognize epitopes in holes in the glycan shield that covers the trimer. Here, we added glycans to block the most immunogenic neutralization epitopes on BG505 and B41 SOSIP trimers. In addition, we removed selected other glycans to open new holes that might expose new immunogenic epitopes. We immunized rabbits with the various glycan-modified trimers and then dissected the specificities of the antibody responses. Thus, in principle, the antibody response might be diverted from one site to a more cross-reactive one, which would help in the induction of broadly neutralizing antibodies by HIV-1 vaccines based on envelope glycoproteins.

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