Vaccine immunogen design
Many pathogenic viruses and cancer cells cover themselves in an extensive shield of sugars, also known as glycans, as a mechanism to evade the adaptive immune response, particularly antibodies. These glycans are added post-translationally by host cell enzymes, and so are recognised as 'self' by the immune system. This is an evolved strategy to avoid the immune response attacking the host (autoimmunity), but as a consequence results in weak or absent anti-viral or anti-cancer antibody responses against these otherwise potential target structures. We are applying novel approaches, in collaboration with the chemistry department, based on design of semi-synthetic glycoprotein conjugates. These designed glycoconjugates are able to break tolerance against these self-like structures, implying that this approach might be valuable for targeting highly glycosylated viruses such as HIV-1 and cancer cells by active vaccination.