Zika: Development of a type specific Zika virus antibody assay for use in Brazil

Lead Research Organisation: University College London
Department Name: UNLISTED

Abstract

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Technical Summary

The emergence and rapid spread of Zika virus (ZIKV) in Latin America, with possible links to
Guillain Barré Syndrome (GBS) and clusters of microcephaly has led WHO to announce a
Public Health Emergency of International Concern on 1st February 2016 (1, 3, 7.). Currently,
diagnosis of acute disease is largely based on virus genome detection. There are no reliable
serological assays which can be used to assess exposure, and therefore contribute to risk
assessment for individual pregnant women or population susceptibility, highlighting the
urgent clinical and public health need to develop a highly specific serological assay for ZIKV.
Affordable and reliable serological tools that can be produced locally, at scale and used
outside reference laboratories, must be part of a rapid emergency response to a newly
emerging infection. Flavivirus serology is notoriously challenging because of antigenic cross
reactivity between different flaviviruses including Dengue 1 to 4 which have circulated widely
in South America in the last 20 years. We intend primarily to develop an enzyme
immunoassay (EIA) for the detection of anti-ZIKV IgG in a competitive format using native
viral antigens, a methodology optimal for distinguishing serological responses to very closelyrelated
viruses. Our direct links, exchange programmes and longstanding relationships with
public health and transfusion centres in Brazil enable us to directly implement local field
assessments and embed a local production capability in country, working through existing
collaborations at the heart of the Brazilian public health system.
 
Description Better diagnostics
Geographic Reach South America 
Policy Influence Type Participation in a guidance/advisory committee
 
Description Public health England pipeline fund
Amount £100,000 (GBP)
Organisation Public Health England 
Sector Public
Country United Kingdom
Start 04/2018 
End 03/2019
 
Title Methods for detecting antibody to ZIKA 
Description The development of a capture assay for ZIKA antibody opens up the possibility of using oral fluid for sero-epidemiological studies. Modification of the conjugate which is usually enzyme-linked viral antigen, converts these tests into sensitive and specific assays. Offers have been made for collaboration for oral fluid testing both in Sao Paulo and in the geographical disposition of countries within the Caribbean. The daba assay has a considerable advantage over other published techniques of sensitivity and, given the alteration of the conjugate a much enhanced specificity over any other commercial assay. These attributes make it more suitable for use than the commercial indirect immunoassays such as Euroimmune. 
Type Of Material Technology assay or reagent 
Year Produced 2018 
Provided To Others? No  
Impact We hope that these various formats will allow local development of serological kits in those countries that need access to secure ZIKA serology. Further field trials are necessary and will occur once the funding is available in April 2018. 
 
Title Preliminary studies 
Description The range of ZIKA diagnostics described elsewhere are currently in a stage of investigation use by colleagues both in Rio and São Paulo. Data is currently being collected on the performance these assays in their final modified conjugate phase. 
Type Of Material Database/Collection of data 
Year Produced 2018 
Provided To Others? No  
Impact Important information on sensitivity and specificity 
 
Description Prof Davide Corti 
Organisation HUMABs Biomed, Bellinzona,Switzerland
Country Switzerland 
Sector Private 
PI Contribution A collaboration between Prof Davide Corti, HuMabs (Humabs BioMed SA, Via Mirasole 1, 6500 Bellinzona, Switzerland) and PHE which began in autumn of 2016 has been very productive. Using specific human monoclonal antibodies, derived from recovered individuals infected with Zika (Stettler K et al., 2016, Science Aug 19, 353: 823-6 ) against conserved epitopes on Zika NS1 and Env we have modified a prototype assay (Blocking of Binding assay [BOB]) developed by Corti and colleagues, and reformatted this into a one-step simultaneous assay with HRPO-labelled antibody and stabilised NS1 Ag on the solid phase .
Collaborator Contribution collaboration on kit development
Impact Kit development
Start Year 2016
 
Title "Flavivirus Diagnostic Assay" 
Description This relates to the modification of the constituents in the conjugate to allow only specifically recognise antigen to be captured by the immobilised antibody, whether this is immobilised by an anti-antibody or by specific antigen. The addition of quenching antigens from related but different viruses is perceived to be novel technology when applied to ZIKA serology and has a broader remit in those assays which require a labelled specific antigen acting as conjugate. 
IP Reference GB1719592.6 
Protection Patent application published
Year Protection Granted 2017
Licensed No
Impact This step, uniquely applicable to conjugates in either capture or double antigen bridging assays confers very great enhancements in specificity without losing sensitivity.