Download Monoclonal antibodies for early control of

SGUL/LSHTM MRC London Intercollegiate Doctoral Training Partnership – 2017/18 Additional Studentships – Potential PhD Projects
Title of PhD project
Monoclonal antibodies for early control of Chikungunya
disease outbreaks
Supervisor
Professor Julian Ma
SGUL
Co-Supervisor
Dr Pascal Drake
SGUL
Brief description of project
Chikungunya (CHIK) fever is an emerging global infection,
characterised by debilitating polyarthralgia that can persist for
months. A 2004 Kenyan outbreak spread through Africa,
much of Asia and parts of Southern Europe resulting in ~
6.5M cases. In 2013, another outbreak led to ~ 1.8M cases
throughout the Caribbean, Central and South America
including almost 0.5M cases in North America. PHE
diagnoses ~100 UK cases/year. There is currently no
licensed vaccine or effective antiviral treatment.
This project will help to develop new tools that are urgently
required to combat CHIK. Specifically, we will examine the
potential role of neutralising monoclonal antibodies (mAbs) in
the treatment and prevention of disease. Passive
immunisation is an important means of controlling infection
and remains vital for some diseases in resource-poor regions
of the world, as recently illustrated by the use of ZMapp
antibodies against Ebola. mAbs can be highly specific and
potent and provide immediate protection in patients
irrespective of their immune status, but they are expensive
and therefore not feasible as a treatment option in developing
regions.
The aims are:
• to identify a panel of anti-CHIK virus broadly neutralising
mAb candidates and map their antigenic epitopes;
• antibody engineering will be designed to enhance
functionality; to express the mAbs using a plant-based
manufacturing platform, appropriate for a developing country
product;
• to identify a cocktail of mAbs to provide broad protection
against prevalent strains and avoid escape emergence;
• to assess protective efficacy of the mAbs against viral
challenge, pharmacokinetics and the immune response to
therapeutic anti-CHIKV mAbs in a transgenic animal CHIK
model.
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SGUL/LSHTM MRC London Intercollegiate Doctoral Training Partnership – 2017/18 Additional Studentships – Potential PhD Projects
Particular prior educational
requirements for a student
undertaking this project
This is a challenging project with co-supervision on two
research sites. The student undertaking this project will need
to have had more than 3 months experience working in a
research laboratory environment.
Good aseptic technique will be an advantage.
Skills we expect a student
to develop/acquire whilst
pursuing this project
This project involves a close collaboration between SGUL
and Professor Roger Hewson (Public Health England,
Porton) who will also be a supervisor for the project. The
student will therefore experience research at two different
institutions. They will acquire skills in whole organism
physiology, as a major part of this project involves in vivo
assessment of monoclonal antibody treatment regimes in a
murine challenge model, and the murine response to mAb
treatment. These studies will be performed in containment
level III facilities at Porton. The student will assist and receive
training from animal staff who are experienced at CL3 animal
work. Therefore, he/she will be required to obtain a home
office licence for animal work. Specific containment level III
training will be provided. This will include a range of key
virology skills to work with CHIK virus, such as culture
techniques, plaque assay and neutralisation tests.
The student will also gain a breadth of experience in
molecular biology and antibody engineering, plant
biotechnology, immunology and immunoassays and protein
purification.
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