Specific Detection of Antibodies to Emerging and Established Arboviruses Including Zika Virus

Abstract Zika virus ZIKV infection is currently an epidemic in the western hemisphere It is a WHO declared Public Health Emergency of International Concern since February due to the association of ZIKV infection with microcephaly and other neurologic abnormalities in babies infected in utero and with Guillain Barre syndrome in infected adults An estimated four million ZIKV infections have occurred in the Americas in and over two billion people live in areas conducive to mosquito borne transmission of ZIKV worldwide To date autochthonous ZIKV infection has been reported in over countries in the western hemisphere including the US protectorate Puerto Rico and state of Florida There is a clear need for accurate and practical methods of detecting ZIKV infection as well as for the development of therapeutic agents and vaccines to combat the associated disease Detection of ZIKV infection is hampered however by the cross reactivity of anti ZIKV antibodies with other arboviruses present in the same areas including DENV and CHIKV and visa versa Specifically neutralization based serodiagnostic tests notably plaque reduction neutralization tests PRNT cannot cleanly distinguish between seropositivity to different members of this set of arboviruses perhaps because antibodies directed at neutralizing epitopes tend to be cross reactive In this application we propose an innovative and comprehensive method for discovering targets of non cross reactive antibodies to emerging and established arboviruses and propose to begin with ZIKV due to the international public health emergency created by this virus Specific Detection of Antibodies to Emerging and Established Arboviruses Including Zika Virus Narrative Zika virus infection is currently an epidemic in the western hemisphere The World Health Organization has declared it a Public Health Emergency of International Concern due to the association of Zika virus infection with microcephaly in babies and with Guillain Barre syndrome in adults An estimated four million Zika virus infections have occurred in the Americas in and over two billion people live in areas conducive to mosquito borne transmission of Zika virus worldwide Indigenous Zika virus infection has been reported in over countries in the western hemisphere including the US protectorate of Puerto Rico and state of Florida There is a clear need for accurate and practical methods of detecting Zika virus infection as well as for the development of therapeutic agents and vaccines to combat the associated disease Detection of Zika virus infection is hampered however by the cross reactivity of anti Zika virus antibodies with other viruses present in the same areas including dengue virus and chikungunya virus In this application we propose an innovative and comprehensive method for specifically detecting Zika virus infection an important step in combatting this international health emergency