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.

Networks of HIV-1 Envelope Glycans Maintain Antibody Epitopes in the Face of Glycan Additions and Deletions

“…While it is impossible to completely unpick the impact of the proline mutation and the glycan addition, we note that the glycan knockins were antigenically similar to the parental protein. The results highlight the importance of characterizing the glycosylation of all candidate immunogens in depth ( Behrens et al., 2017b ).…”

Differential processing of HIV envelope glycans on the virus and soluble recombinant trimer

“…Many bnAbs, have epitopes that are both protein and glycan dependent 3 , 4 , while others have features that accommodate bulky glycans adjacent to their epitopes 5 . Thus, it is believed that Env-based immunogens with glycosylation matching authentic viral Env will be required at some stage in an overall vaccine strategy 6 .…”

Engineered human mesenchymal stem cells as new vaccine platform for COVID-19

“…The research and development route based on stem cells proposed in this report can realize the presentation of antigen proteins of multiple targets by virtue of the feature of presenting and secreting part of the novel coronavirus antigen protein. Most importantly, some of the novel coronavirus proteins mediated and secreted by stem cells will be modified, like glycosylation [15] and acetylation, mimicking the virus protein modification in vivo, which can well simulate response increase the success rate of onetime immunity [16] . It was reported that mice strains maintained in the laboratory are not susceptible to SARS-CoV-2 infection [17] , due to the variation of ACE2 receptor for virus entry [18,19] .…”