Glycosylation profiling to evaluate glycoprotein immunogens against HIV-1

ABSTRACT

Introduction: Much of the efforts to develop a vaccine against the human immunodeficiency virus (HIV) have focused on the design of recombinant mimics of the viral attachment glycoprotein (Env). The leading immunogens exhibit native-like antigenic properties and are being investigated for their ability to induce broadly neutralizing antibodies (bNAbs). Understanding the relative abundance of glycans at particular glycosylation sites on these immunogens is important as most bNAbs have evolved to recognize or evade the dense coat of glycans that masks much of the protein surface. Understanding the glycan structures on candidate immunogens enables triaging between native-like conformations and immunogens lacking key structural features as steric constraints limit glycan processing. The sensitivity of the processing state of a particular glycan to its structural environment has led to the need for quantitative glycan profiling and site-specific analysis to probe the structural integrity of immunogens.

Areas covered: We review analytical methodologies for HIV immunogen evaluation and discuss how these studies have led to a greater understanding of the structural constraints that control the glycosylation state of the HIV attachment and fusion spike.

Expert commentary: Total composition and site-specific glycosylation profiling are emerging as standard methods in the evaluation of Env-based immunogen candidates.

KEYWORDS:

• HIV
• vaccine design
• mass spectrometry
• glycosylation
• envelope
• Env
• glycomics
• glycoproteomics

Acknowledgments

We thank Prof. David Harvey, Prof. Dennis Burton, Prof. Ian Wilson FRS, and Prof. Raymond A. Dwek FRS for their support and helpful discussions.

Declaration of interest

A.-J. Behrens is a recipient of a Chris Scanlan Memorial Scholarship from Corpus Christi College. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This work was supported by grants from the Scripps Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (1UM1AI100663) and the International AIDS Vaccine Initiative (IAVI) and the IAVI Neutralizing Antibody Center CAVD grant (Glycan characterization and Outer Domain glycoform design; OPP1084519). This project has received funding from the European Union’s Horizon 2020 Research and Innovation Programme under grant agreement No. 681137.