The ability to design efficacious vaccines for many diseases has been hindered by existing sequence diversity in pathogen proteins and by newly-acquired mutations that enable escape from adaptive immune responses. To address these limitations, we have developed an approach for nanopatterning protein antigens to focus the immune response on conserved protein regions. This approach combines the site-specific incorporation of non-canonical amino acids into proteins with chemical modification with polyethylene glycol (PEG) or other molecules. We will first demonstrate the efficacy of the approach using green fluorescent protein (GFP) as a model antigen. We will also discuss our attempts to apply this approach to the design of improved Zika vaccines. Zika fever – caused by the Zika virus (ZIKV), a member of the Flaviviridae family – attracted global attention after its outbreak in 2015. The link between ZIKV infections and the possible development of severe central nervous system disorders was particularly troubling, making the creation of a Zika vaccine a pressing issue. While efforts to develop such vaccine are underway, current efforts do not address a major potential problem with flaviviral vaccines – antibody-dependent disease enhancement (ADE). To prevent ADE, it is imperative to elicit primarily neutralizing and ZIKV-specific antibodies. To that end, we will describe the design of a ZIKV vaccine based on domain III (DIII) of the viral envelope protein (E). Recent reports have described three different antibody epitopes on DIII - one of which is a non-neutralizing epitope due its hidden position in the context of the Zika virion. We will describe the use of nanopatterning to tune the recognition of DIII by the immune system. By chemically modifying the protein surface, we aim to direct the immune response away from epitopes that will not contribute to viral neutralization. We will also describe the multivalent presentation of the nanopatterned antigens from scaffolds in order to enhance immunogenicity. The approach described in this work should enable the elicitation of broadly protective antibodies against a wide range of pathogens and toxins.

Nanopatterning protein antigens to refocus the immune response

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.