Zika Virus Vaccines based on Nanoscale Constructs Presenting the Envelope Protein

Georgia Institute Of Technology, Atlanta GA

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Abstract

The objective of the proposed work is to develop and characterize vaccines based on virus-like particles (VLPs) presenting multiple copies of the Zika virus (ZIKV) envelope (E) protein. The ongoing ZIKV epidemic constitutes a serious public health problem with the linkage to an increase in reported cases of congenital microcephaly causing particular concern. An effective vaccine against ZIKV is therefore a critical unmet need. Moreover, given the necessity of administering such a vaccine to pregnant women, it would be useful to develop alternatives to vaccines based on live attenuated viruses as well as to explore vaccines that may confer protection without the use of adjuvants. In previous work, we have designed nanoscale scaffolds presenting other viral glycoprotein antigens that elicited protective immune responses in vivo. We also have expertise in testing the efficacy of vaccines and monoclonal antibodies in vivo. The first aim of the proposed work is to design and characterize nanoscale constructs based on VLPs presenting monomers of the ZIKV E protein. The second aim is to stabilize dimers of the ZIKV E protein and to characterize and optimize the immunogenicity of VLPs presenting the dimers. We anticipate that this approach will yield nanoscale constructs that present ZIKV antigens in a controlled orientation and elicit high titers of neutralizing antibodies. The proposed studies will not only help us identify promising candidates that can be moved forward into more extensive pre-clinical studies, but will also yield reagents that will be useful for characterizing the human antibody response to ZIKV infection.