PMC:7108637 / 76491-79437 JSONTXT

{"project":"2_test","denotations":[{"id":"29579213-22265860-45167991","span":{"begin":527,"end":531},"obj":"22265860"},{"id":"29579213-23142589-45167992","span":{"begin":548,"end":552},"obj":"23142589"},{"id":"29579213-25203219-45167993","span":{"begin":572,"end":576},"obj":"25203219"},{"id":"29579213-23474232-45167994","span":{"begin":1212,"end":1216},"obj":"23474232"},{"id":"29579213-27630242-45167995","span":{"begin":1690,"end":1694},"obj":"27630242"},{"id":"29579213-28202756-45167996","span":{"begin":1706,"end":1710},"obj":"28202756"},{"id":"29579213-20660197-45167997","span":{"begin":1907,"end":1911},"obj":"20660197"},{"id":"T44207","span":{"begin":527,"end":531},"obj":"22265860"},{"id":"T73480","span":{"begin":548,"end":552},"obj":"23142589"},{"id":"T31115","span":{"begin":572,"end":576},"obj":"25203219"},{"id":"T13524","span":{"begin":1212,"end":1216},"obj":"23474232"},{"id":"T81652","span":{"begin":1690,"end":1694},"obj":"27630242"},{"id":"T49258","span":{"begin":1706,"end":1710},"obj":"28202756"},{"id":"T29217","span":{"begin":1907,"end":1911},"obj":"20660197"}],"text":"Being the components of viral particles exposed to the extracellular environment, viral envelope glycoproteins serve as major targets for vaccine development; however, protein sequence variability within and across strains, high mutation rate, as well as enormous heterogeneity of glycan structures makes it very difficult to identify immunogens evoking universal reactivity. Various expression systems are used for production of subunit vaccine candidates, such as bacteria, yeast, plant, insect and mammalian cell lines (Cox 2012; Kushnir et al. 2012; Redkiewicz et al. 2014). While some glycosylation types can be replicated in insect and mammalian cells, yeast cells will not carry out mucin type O-glycosylation and proteins produced in bacterial cells will also lack N-glycans. Even mammalian expression systems may lack the required glycosyltransferase repertoire to glycosylate relevant sites and build up relevant structures. Although there are many successful examples of vaccines produced in aforementioned systems, there is quite a number of infectious diseases that still lack vaccine coverage due to failure of vaccine candidates to induce adequate and lasting immune responses (Grimm and Ackerman 2013). Therefore, cell lines closer to the natural host cell type should be explored to more accurately reproduce the overall protein structure, modifications, and exposed antigenic sites for the primed immune system to be able to neutralize the naturally encountered antigen. Recently, efforts are being made to identify consensus glycosylation patterns, as well as production platforms leading to elicitation of desired immune responses and pathogen neutralization (Li et al. 2016; Go et al. 2017). In contrast to fast mutating RNA viruses, DNA viruses, including herpesviruses, have relatively stable genomes and rely on other means for counteracting the host’s immune system (Sanjuan et al. 2010). It is therefore conceivable, that vaccine development should be less challenging for DNA viruses. However, most of herpesvirus-targeted subunit vaccines have failed so far. A recently developed HSV-2 vaccine lacking the main neutralizing antibody target is, however, showing great promise in mice. This vaccine evokes production of non-neutralizing antibodies to other envelope glycoproteins on infected cells, stimulating cellular NK cell immunity through engagement of Fcγ receptors (Petro et al. 2015). In conclusion, glycans on viral envelope glycoproteins have a tremendous impact on recognition by the host, and glycosylation heterogeneity makes it very difficult to identify universal vaccine candidates. While experimental evidence is key, development of accurate bioinformatic tools to predict glycosylation and likely mutation patterns would be of big value for vaccine research. This should become possible once a substantial number of viral strains are sequenced and analyzed for glycan modifications in native contexts."}