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Volume 9 Supplement 2

AIDS Vaccine 2012

  • Poster presentation
  • Open Access

Transforming epitope-specific gp120 monomer-based probes into immunogens with N-linked glycan masking

  • 1,
  • 1,
  • 1,
  • 1 and
  • 1
Retrovirology20129 (Suppl 2) :P318

https://doi.org/10.1186/1742-4690-9-S2-P318

  • Published:

Keywords

  • Immune Response
  • Infectious Disease
  • Cancer Research
  • Potential Complication
  • Residue Position

Background

HIV-1 gp120 monomer-based probes have been used for the identification of broadly neutralizing antibodies. Such probes could represent starting points in the design of HIV-1 immunogens, though efforts must be made to silence immune responses directed toward non-neutralizing epitopes. One possible approach would be to mask these epitopes by introducing N-linked glycan. A potential complication to such an approach is glycan occupancy: although N-linked glycosylation generally occurs at N-X-T/S sequons, many such sequons are not occupied.

Methods

A computational protocol was developed to identify the putative positions for insertion of N-linked glycan on the gp120 surface. The first step involves the identification of residue positions on the gp120 surface where the insertion of the N-X-T/S sequon is predicted as energetically-tolerable. The second step involves the application of NGlycPred, a Random Forest-based predictor, to predict the glycan occupancy at the inserted sequons.

Results

The glycan occupancy prediction of the protocol is highly correlated to validated N-X-T sequon insertion designs. Multiple sequon insertions to gp120 monomer-based probes were generated based on the protocol.

Conclusion

A computational protocol was implemented to identify putative sites for insertion of N-X-T/S sequons with improved likelihood of glycan occupancy. The protocol is applicable to the design of N-linked glycans for masking non-neutralizing antibody epitopes on gp120-based probes as well as other immunogen candidates.

Authors’ Affiliations

(1)
National Institutes of Health/NIAID, Bethesda, MD, USA

Copyright

© Chuang et al; licensee BioMed Central Ltd. 2012

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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