REVIEW article
Front. Immunol.
Sec. Vaccines and Molecular Therapeutics
This article is part of the Research TopicRole of Glycosylation in Vaccine Design: Modulating the Targeting of Pathogen Recognition Receptors and Shaping Adaptive ImmunityView all articles
Glycan masking in immunogen design: computational and experimental methods
Provisionally accepted
Gustavo Araiza1Josuel Morel1
Minh H. Tran1Shan Jiang1
Sean Murray2Emika Miyamoto1Hannah Vogts3Kyle L. Brown1,4Jens Meiler1,5
Cristina Elisa Martina1*- 1Vanderbilt University, Nashville, United States
- 2Belmont University, Nashville, United States
- 3The University of Iowa, Iowa City, United States
- 4Vanderbilt University Medical Center, Nashville, United States
- 5Universitat Leipzig, Leipzig, Germany
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Epitope-focused vaccine design aims to improve upon existing immunization strategies by eliciting immune responses against specific epitopes targeted by known therapeutic antibodies. One of the techniques in epitope-focused immunogen design is glycan masking, in which sugars are used to hide epitopes on the protein of interest that are associated with low therapeutic potency. Here, we provide a detailed overview of the computational and experimental techniques associated with glycan masking for immunogen design at a biochemical and biophysical level. We will cover well-established and emerging in silico methods for predicting and engineering glycosylation sites. Additionally, we will discuss expression and validation of glycosylated immunogens in vitro. We hope this review will be a useful overview for scientists interested in performing glycan masking in their field of research.
Keywords: Epitope-focused vaccine design, glycan masking, Glycan shield, Glycoengineering, immunogen design, N-linked glycosylation, Protein-glycan modeling, reverse vaccinology
Received: 16 Oct 2025; Accepted: 12 Dec 2025.
Copyright: © 2025 Araiza, Morel, Tran, Jiang, Murray, Miyamoto, Vogts, Brown, Meiler and Martina. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Cristina Elisa Martina
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.