Dr Linda Murungi
Dr Linda Murungi, KEMRI Wellcome Trust Research Programme, Kenya
Host institution: Liverpool School of Tropical Medicine, UK
Working towards better vaccines in the fight against malaria
Functional human monoclonal antibodies as tools for defining the merozoite targets of protective immunity against P. falciparum malaria.
I work on how the human immune system faces up to the challenges of malaria. By understanding the complex warfare between the two, we are more likely to achieve the elusive goal of an effective vaccine to protect people from this deadly disease.. It is on this area of research that I recently received my PhD from the Open University (UK). It fits with my broader interests in the discovery and development of vaccines against pathogens that are responsible for diseases that disproportionately affect people living in developing countries.
To address this aim, I will screen sera from malaria-exposed adults in several tests (assays) to identify individuals with the most potent antibodies. Thereafter, recombinant monoclonal antibodies will be generated from memory B-cells of these individuals and characterized for functional activity in the same assays. I will then identify the proteins targeted by these antibodies using immunoproteomic approaches and mass spectrometry. This unique approach has the potential to accelerate the discovery of second generation malaria vaccine targets. The antibodies could also be used for immunotherapy.
During my placement at the Liverpool School of Tropical Medicine with Dr Britta Urban (Reader in Biomedical Science), I will gain hands-on experience in single-cell sorting, RT-PCR, expression cloning, production, purification and quantification of human monoclonal antibodies. I will also tap into her expertise in analysis and interpretation of antibody sequence data using modern bioinformatics tools. After the placement, I will receive support to consolidate the pilot data generated from AREF funding and refine my research question in order to competitively apply for research funding to support my career development
What is a monoclonal antibody?
A laboratory produced molecule that is carefully engineered to attach to specific defects in affected cells (in this case cells infected with the malaria parasite)
Monoclonal antibodies are proteins produced in the laboratory from a single clone of a B cell, the type of cell of the immune system that make antibodies.A key limitation for malaria vaccine development is the lack of immune correlates of protection. (Correlates of immunity/protection to a virus or other infectious pathogens are measurable signs that a person (or other potential host) is immune, in the sense of being protected against becoming infected and/or developing disease. https://en.wikipedia.org/wiki/Correlates_of_immunity/correlates_of_protection.) My project will focus on isolating monoclonal antibodies with demonstrable functional activity and identifying their targets on the parasite.