Zika: Development of a type specific Zika virus antibody assay for use in Brazil
Lead Research Organisation:
University College London
Department Name: UNLISTED
Abstract
Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.
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.
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.
Publications
Balmaseda A
(2017)
Antibody-based assay discriminates Zika virus infection from other flaviviruses.
in Proceedings of the National Academy of Sciences of the United States of America
Pallett SJ
(2022)
Variability in detection of SARS-CoV-2-specific antibody responses following mild infection: a prospective multicentre cross-sectional study, London, United Kingdom, 17 April to 17 July 2020.
in Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin
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. |