KEPHERA DIAGNOSTICS LLC — Department of Health and Human Services SBIR Phase I: NIAID

Description

Project Summary Zika virusuntil recently an obscure mosquito borne flavivirus from Africahas emerged rapidly within the past two years as a major threat to public health in the Western HemisphereHaving traveled across the Pacificit has become endemic in Brazil and is expanding its territory northwards in South and Central AmericaMexico and the Caribbeancarried by a similarly expanding Aedes mosquito populationWhile Zika virus infection is generally relatively benign in the acute stageit is suspected based on growing evidence of causing microcephaly in infants born to infected womenand has been linked to Guillain Barrsyndrome and meningitis in other casesIn addition to transmission by mosquito biteZika can likely be transmitted by sexual contact and through blood transfusionsThe World Health OrganizationWHOhas declared Zika to be an international public health emergencyand the U SCenters for Disease ControlCDCand the U SFood and Drug AdministrationFDAare actively ramping up efforts to prepare for and respond to the threat posed by Zika in the United StatesAccordinglyFDA has advised the temporary deferral of blood donors who have had potential exposure in endemic areas such as Puerto Ricoand has recently approved the use under IND of investigational blood screening assays detecting viral RNAHowevergiven the very short duration of viremiamost individuals exposed to Zika virus are likely to be negative when tested for viral RNAand the only means to detect prior exposure and associated health risks is through serologic tests for antibodies to the virusAs the emergence of Zika as a significant human health threat is so recentthere has been no demand for diagnostic assays until nowand commercial products are either non existent or inadequately validatedThis project addresses the critical need for a clinical diagnostic assay for Zika virus infectionThe need is further exacerbated by the difficulty in distinguishing Zika from Dengue virus infection given that the two viruses are genetically relatedand overlap in mosquito vector and regions of endemicityIn Phase Iwe propose to identify peptide epitopes specific for the Zika virus that will enable development of an ELISA allowing accurate serologic identification of Zika infection in individuals beyond the viremic phasewho may also have had exposure to Dengue or other flavivirusesTo accomplish thiswe will probe overlapping peptide microarrays derived from Zika proteins with serum samples from individuals with Zika or Dengue infectionconfirmed by nucleic acid and immunological assaysLongitudinal sampling from individuals originally identified with acute Zika infection by RNA assays will provide gold standard serum samples with successive IgM and IgG seropositivity for assay development and validationImmunoreactive peptides will be identified and translated into ELISA test formatIn Phase IIwe plan to refine this assay into an FDA clearedmanufactured product for in vitro diagnosis of infected individuals and management and counseling of blood donors