New approaches to glycan-based viral vaccine design
Glycosylation is one of the most common post-translational protein modifications, and has been harnessed by many pathogens to evade the adaptive immune response. Use of asparagine (N)-linked glycans on viral glycoproteins is of particular relevance to neutralizing antibody evasion by HIV-1, influenza A and hepatitis C viruses. Because glycans are added to viral proteins by host cell machinery, they are seen as ‘self’ by the host and therefore tolerance mechanisms generally prevent robust immune responses to them. However under certain conditions viral glycans can become immunogenic, and this is seen in many of the most potent neutralizing antibodies isolated against HIV-1. Thus a strategy to enhance the immunogenicity of selected glycans might facilitate the elicitation of neutralizing antibodies to HIV-1 and other viruses as part of a vaccine strategy. With our collaborators in the Oxford University Chemistry Department, we have recently demonstrated that coupling of semi-synthetic glycans to proteins via non-natural linkages leads to high levels of glycan-specific antibody production. Moreover, these antibodies are of IgG subclass, implying T cell help for class switch and somatic hypermutation. The current project is to understand the mechanism of enhanced glycan immunogenicity observed to non-naturally linked glycans, and to apply this knowledge to designing neutralizing antibody-based vaccines against HIV-1 and potentially to other human pathogenic viruses. The student will learn techniques including: molecular biology and gene cloning; protein molecular modeling; protein expression, purification and characterization; preparation and characterization of semi-synthetic glycans; post translational modification of proteins; evaluation of antibody and T cell responses to modified viral glycoproteins.
4 Year DPhil Prize Studentships cover University fees, a tax free stipend of ~£17,009 pa, and up to £5,300 pa for research costs and travel. The competition is open to applicants from all countries. See View Website for full details and to apply.
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FTE Category A staff submitted: 223.80
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