Zika: Harnessing plant power for rational design of immunogens for use in diagnostic assays
Lead Research Organisation:
University of Nottingham
Department Name: UNLISTED
Abstract
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Technical Summary
Laboratory confirmation of Zika virus infection is complicated by cross-reactivity of antibodies
with other members of the same virus family. This includes Dengue virus, which is
transmitted by the same species of mosquito as Zika and therefore also infects people in the
same regions where Zika virus is currently emerging. Therefore, it is important to be able to
distinguish between antibodies that have been raised against a previously encountered virus
and antibodies that indicate a recent or current virus infection. A traditional approach to
address this problem, which also occurs for Dengue and Japanese encephalitis virus in Asia,
is to test for antibodies generated early in the response to infection (IgM) to two viruses in
parallel. The virus that gives the highest value in the MAC-ELISA is taken to be the most
recently encountered virus. In the past decade, plant-expression of proteins, including viruslike
particles, has really come of age. This powerful technology will be harnessed in the
current project to generate more specific diagnostic reagents to allow antibodies to Zika virus
to be distinguished from antibodies generated to other flaviviruses such as Dengue.
with other members of the same virus family. This includes Dengue virus, which is
transmitted by the same species of mosquito as Zika and therefore also infects people in the
same regions where Zika virus is currently emerging. Therefore, it is important to be able to
distinguish between antibodies that have been raised against a previously encountered virus
and antibodies that indicate a recent or current virus infection. A traditional approach to
address this problem, which also occurs for Dengue and Japanese encephalitis virus in Asia,
is to test for antibodies generated early in the response to infection (IgM) to two viruses in
parallel. The virus that gives the highest value in the MAC-ELISA is taken to be the most
recently encountered virus. In the past decade, plant-expression of proteins, including viruslike
particles, has really come of age. This powerful technology will be harnessed in the
current project to generate more specific diagnostic reagents to allow antibodies to Zika virus
to be distinguished from antibodies generated to other flaviviruses such as Dengue.
People |
ORCID iD |
| Description | Further collaboration with USP, Brazil |
| Organisation | Universidade de São Paulo |
| Country | Brazil |
| Sector | Academic/University |
| PI Contribution | I was able to visit the CoI (Professor Luis Ferreira) on the original award (MC_PC_15085) as a result of a University-sponsored trip to Brazil in 2019 - this was the first time we had met in person. Through this visit, we were able to re-ignite enthusiasm for collaboration and Professor Ferreira's postdoctoral researcher was able to pay a short visit to our labs in November 2019 to receive training in next-generation phage display applied to identify peptides that can distinguish between envelope domain III of Zika and dengue viruses. The plan had been for the PDRA to return in 2020 to complete this work after an application for travel funding to FAPESP with matched funding for consumables provided by the University of Nottingham School of Veterinary Science. Unfortunately, the COVID pandemic meant that the funding was withdrawn. We are now in the process of arranging for the PDRA to return during the summer of 2022 (funding for this visit has been secured). In addition, funding has just been awarded by the Department of Health and Social Care's (DHSC) UK Vaccine Network (UKVN), delivered by Innovate UK to develop a new DNA vaccine platform to induce safe protective immunity from Zika. The research, being led by Dr James Dixon in the University of Nottingham's School of Pharmacy and Biodiscovery Institute (BDI) builds on our experience in developing a DNA vaccine for COVID-19 with Innovate UK funding. It also further involves collaboration with Professor Luís CS Ferreira and colleagues at the University of Sao Paulo's Vaccine Development Laboratory in Brazil. |
| Collaborator Contribution | The visiting PDRA brought with them peptides they had expressed in Brazil for use in next generation phage display panning experiments in our labs. |
| Impact | No outputs to date - we have been waiting for COVID-19 situation to have stabilized. |
| Start Year | 2019 |
| Description | Joint PhD studentship with Moredun Institute |
| Organisation | Moredun Research Institute |
| Country | United Kingdom |
| Sector | Charity/Non Profit |
| PI Contribution | This was a joint PhD student for which the School of Veterinary Medicine and Science, University of Nottingham contributed 50% of the student stipend, fees and consumables. I directly supervised the student with Professor Kevin Gough, School of Veterinary Medicine and Science, University of Nottingham acting as secondary supervisor. The project benefitted from experience gained during the previous award (MC_PC_15085). |
| Collaborator Contribution | This is a joint PhD student for which the Moredun Research Institute contributed 50% of the student stipend, fees and consumables. The supervisor at the Moredun Research Institute contributed samples and expertise. |
| Impact | The PhD student appointed on this collaboration started in January 2018. They were due to complete their period of registration in December 2020, but due to the impact of COVID, their period of registration was extended. They recently submitted their thesis and had their PhD viva - they are currently addressing corrections. They have been appointed as a researcher on a BBSRC-funded project that further extends the techniques developed during their PhD. |
| Start Year | 2017 |