Glycosylation as a tool for rational vaccine design

Abstract

The discovery of broadly neutralizing antibodies that can neutralize multiple strains or subtypes of a pathogen has renewed interest in the development of broadly protective vaccines. To that end, there has been an interest in designing immunofocusing strategies to direct the immune response to specific, conserved regions on antigenic proteins. Modulation of glycosylation is one such immunofocusing strategy; extensive glycosylation is often exploited by pathogens for immune evasion. Masking epitopes on protein immunogens with “self” glycans can also shield the underlying protein surface from humoral immune surveillance. We review recent advances in applying glycosylation as an immunofocusing tool. We also highlight recent interesting work in the HIV‐1 field involving the identification and elicitation of broadly neutralizing antibodies that incorporate glycans into their binding epitopes.

Optimization of the human colorectal carcinoma antigen GA733-2 production in tobacco plants

“…For production of recombinant proteins for vaccine candidates, it is essential to determine glycosylation patterns of the produced recombinant protein (Bosch and Schots 2010;Hariharan and Kane 2020;Van Droogenbroeck et al 2007), because plant-specific N-glycosylation patterns, such as β-1,2-xylose and α-1,3-fucose, which are generated during protein process in Golgi, are often allergenic for mammalian system (Bakker et al 2001;Schoberer and Strasser 2018;Wilson et al 2001). Targeting of recombinant proteins into ER is known to bypass these plant-specific glycosylation patterns (Nausch et al 2012).…”

Human Monoclonal Antibodies against NS1 Protein Protect against Lethal West Nile Virus Infection

“…Alternatively, targeting of other epitopes in NS1 (e.g., the outer surface of wing domain or spaghetti loop) may provide protection without the risk of adverse consequences. Vaccines could be designed to focus the immune response on specific epitope locations, either through design of NS1 immunogens lacking the conserved C-terminal region or by masking these epitopes by adding additional N-linked glycans in a site-specific manner ( 72 – 75 ).…”

Protein engineering strategies for rational immunogen design

“…Glycans are naturally present on viral envelope proteins and play key roles in stability, pathogenicity, and immunogenicity, as well as escape from immune surveillance [82][83][84][85][86][87][88][89][90] . Overall glycosylation patterns can affect antigen processing, delivery into GCs, and breadth of elicited responses [91][92][93][94][95][96][97][98][99][100][101] . The variation in these natural glycosylation patterns in response to immune pressure provides a guide to introduce glycans on rationally designed immunogens 100,102,103 .…”