Smart Biomimetic Nanomaterials for Novel Treatment and Prevention of Viral Infection

Scientific excellence
In combatting infectious disease, biology relies on antibodies which show unrivalled specificity for molecular recognition. There is currently an unmet need to be able to rapidly produce therapeutic neutralising antibodies and vaccines to emergent viruses. We are developing molecularly imprinted polymers (MIPs). MIPs are bespoke polymers that possess the chemical and structural architecture for the specific recognition of a target biomolecule, which may include proteins or viruses. MIPs offer synthetic, stable and economical alternatives to antibodies with ease of mass production.

II. Clear aim and hypothesis
We hypothesise that virus-imprinted MIPs may serve as bio-functional ‘plastic antibodies’ capable of neutralising viruses, which we aim to develop as a novel approach to treat or prevent infection in animals or humans. We further hypothesise that it is possible to use virus-imprinted MIP cavities as moulds to grow polymeric secondary imprints that can serve as antigenic mimics of the original virus and be used as novel prophylactic vaccines.

III. Methodology and innovations
The proposed project will directly test these hypotheses and determine proof-of-concept using a model mammalian virus, bovine viral diarrhoea virus (BVDV). Our preliminary results have demonstrated a highly effective and specific neutralisation of virus infectivity using hydrogel gel-based MIPs. We will now evaluate virus-imprinting of nanoscale MIPs (nanoMIPs) for the efficient production of high bioaffinity materials. The nanoMIPs will be characterized using a range of physical/analytical techniques. The ability of virus-imprinted nanoMIPs to inhibit BVDV infectivity in vitro will be directly compared against monoclonal antibodies (MAbs) and our established virus-imprinted hydrogel MIPs. We will determine the biocompatibility of nanoMIPs with BVDV susceptible cell lines before conducting neutralisation assays in which virus and MIPs are directly applied to cell monolayers. We will investigate the synthesis of secondary nanoMIPs from the primary virus-imprinted nanoMIPs to produce synthetic virus mimics. We will assess and characterise the immunorecognition of secondary nanoMIPs by a panel of BVDV neutralising MAbs using bio-layer interferometry.

IV. Strategic relevance
UCLan is committed to the ‘One Health’ agenda, which is an international interdisciplinary collaborative effort, driven in large part, by the need to address the control of global and emerging viral zoonoses1. Within the next 10 years, the world population is estimated to increase by 1 billion and over half of them will be over the age of 50. Healthcare will need to undergo rapid changes in response to emerging diseases as well as those associated with the inevitable ageing demographic. Our research will provide a solid platform on which to further develop MIPs as a novel class of next-generation therapeutics and vaccines.

V. Interdisciplinarity and fit with relevant DTA programme
The number of people in the UK aged over 75 is currently 1 in 12 will rise to 1 in 7 by 2040. In addition to enjoying retirement, this population will want to continue to be independent and contribute to society through for example, working, building/maintaining relationships and being mobile. Being free of disease or infirmity can facilitate such healthy ageing aspirations. In order to support this and given that the immune response can decline in efficiency with age, there needs to be an evolving programme of readiness for the next outbreak pathogen, thereby rapidly eliminating the threat of a pandemic and thus protecting the ageing demographic. Our proposed work fits within the DTA Applied Biosciences for Health programme combining cutting-edge materials science & technology expertise (Prof. Reddy2-5 and Dr Kulkarni6-7) with complimentary biological expertise in virology and immunology (Dr Graham8-10 and Dr Dennison11-12) to address an important unmet need in vaccinology and to provide a technological platform that could be broadly applied to combat infectious diseases of both humans and animals.

Applications

Applicants must apply using the online form on the University Alliance website at https://unialliance.ac.uk/dta/cofund/how-to-apply/. Full details of the programme, eligibility details and a list of available research projects can be seen at https://unialliance.ac.uk/dta/cofund/

The final deadline for application is Monday 8 October 2018. There will be another opportunity to apply for DTA3 projects in the spring of 2019. The list of available projects is likely to change for the second intake.