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Development of therapeutic monoclonal antibodies for coronaviruses


   Faculty of Health & Medical Sciences

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  Dr E Tchilian, Prof Christine Rollier  No more applications being accepted  Funded PhD Project (Students Worldwide)

About the Project

Respiratory viruses are amongst the greatest threat to global health, with coronaviruses (CoVs) causing three major human epidemics since 2003, including the ongoing SARS-CoV-2 pandemic. While vaccines remain the best strategy to prevent COVID-19, neutralising monoclonal antibodies (mAbs) maybe useful for treating vulnerable populations before or after exposure to SARS-CoV-2. To date, most research efforts for therapeutic use of mAbs have focussed on Spike (S) specific neutralising antibodies and there are a handful of products already authorised for human use.

Most therapeutic mAbs have been tested pre-clinically in small animal models, but this is not always predictive of outcome in humans. There is, therefore, a need for a large animal model in which mAbs selected on the basis of in vitro assays can be further studied to help in selecting promising mAbs targets and determining how best to administer them in clinical trials. Pigs may provide such a model, we have already shown this specie to be very useful for testing influenza mAbs (1, 2). They are large animals physiologically, anatomically, and immunologically more similar to humans than small animals (3, 4). Pigs are natural hosts for several CoVs with porcine respiratory CoV (PRCV) exhibiting common features with SARS-CoV-2. Other porcine or related CoVs are a zoonotic threat, with a novel Alphacoronavirus and porcine Deltacoronavirus being detected in humans. We have established an in vivo porcine PRCV model in which lung pathology resembles the human (5).

In this project, the successful candidate will isolate PRCV specific mAbs, characterise their specificity, functional activity in vitro and test their therapeutic utility in vivo. This will give further insights into CoV infections and how to generate and administer novel efficacious therapies against CoVs in humans.

A 3.5-year funded studentship open to home and international students starting in October 2022.

More information on the School of Biosciences and Medicine and The Pirbright Institute.

Entry requirements

A First or Upper Second-Class Honours degree from the UK (or equivalent qualification from international Institutions) or Masters degree in a relevant subject area.

English language requirements: An IELTS Academic of 6.5 or above with 6 in each individual category (or equivalent qualification from other agencies).

How to apply

Applications should be submitted via the online application portal for Biosciences and Medicine PhDs. In addition to your formal application, please also email Dr Elma Tchilian ([Email Address Removed]) or Professor Christine Rollier ([Email Address Removed]) with your application.


Funding Notes

Funding includes stipend, home registration fees and a research grant. Note that due to the way this project is funded, an international student appointed to this project would be required to pay 50% of the difference between the normal registration fee for home and international students. This amounts to approximately £9500 for the academic year 2022-23, with annual incremental increases for subsequent years.

References

References:
1) McNee A et al, Establishment of a pig influenza challenge model for evaluation of monoclonal antibody delivery platforms (2020). J Immunology 205(3):648-660.
2) Holzer B et al, Protective porcine influenza virus-specific monoclonal antibodies recognize similar haemagglutinin epitopes as humans (2021). PLoS Pathog. 17(3):e1009330
3) Martini V et al, Simultaneous aerosol and intramuscular immunization induces powerful protective local T cell and systemic antibody immune responses in pigs (2021). J Immunol. 206(3):652-663
4) Tan TK et al, A COVID-19 vaccine candidate using SpyCatcher multimerization of the SARS-CoV-2 spike protein receptor-binding domain induces potent neutralising antibody responses (2021). Nat Commun. 12(1):542
5) Jung K et al, Altered Pathogenesis of Porcine Respiratory Coronavirus in Pigs due to Immunosuppressive Effects of Dexamethasone: Implications for Corticosteroid Use in Treatment of Severe Acute Respiratory Syndrome Coronavirus (2007). J Virology 81, 13681-13693.
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