(81b) Developing a Modular Virus-like Particle Vaccine Platform for Viral Diseases

Recent Zika outbreaks in French Polynesia and Brazil have brought the association between the Zika virus and multiple serious conditions including birth defects such as microcephaly and the neurological condition known as Guillain-Barré Syndrome to the worldâ??s attention. The Zika virus is spread to people primarily through the bite of an Aedes ageypti mosquito (the same mosquito that spreads dengue and yellow fever) and has symptoms similar to many other diseases including fever, rash, joint pain, and red eyes. Because the symptoms of Zika virus are mild and resolve within less than a week, people do not generally require hospitalization and cases are not reported, making Zika infection difficult to track. Currently the only way to prevent Zika infection is to avoid mosquito bites and relies strongly on regular patient compliance. A prophylactic vaccine is especially necessary in the case of a virus like Zika where the consequences are potentially severe but symptoms are typically mild and overlap with many other common illnesses.

Here we discuss the development of a modular, virus-like particle based vaccine platform in the context of our work to address the need for a prophylactic Zika vaccine. Through cell-free protein synthesis, we can produce and stockpile an engineered virus-like particle. This virus-like particle can be conjugated to a relevant antigen (Protein E Domain III for our Zika vaccine candidate) using click chemistry. The virus-like particle scaffold allows for multivalent display of the relevant antigen in a manner that mimics presentation on the natural virus. Multiple orientations of the antigen on the virus-like particle scaffold are easily evaluated by creating antigen variants with a non-natural amino acid incorporated in different positions within the protein. Additionally, innate immune stimulators will be co-attached to the virus-like particle to boost the immune response to the antigen by acting as a non-denaturing adjuvant. This platform is easily translated to other diseases, including the influenza and HIV efforts currently underway in our lab.