Artikel
Recombinant human anti-malarial monoclonal antibodies – a technology platform
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Veröffentlicht: | 29. Januar 2014 |
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Gliederung
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Despite an enormous effort during the last years, a protective vaccine against malaria is still lacking. It becomes more and more evident, that an exact profile of both the vaccine elicited and the natural immune response against Plasmodium falciparum infection is needed.
As part of a Fraunhofer Malaria Foundation Project, a Technology Platform for the isolation of human monoclonal antibodies from semi-immune donors living in a holoendemic setting has been established at the Fraunhofer IME in Aachen, Germany.
The technology is based on a five step process including: (1) the characterization of the antibody source by screening the serum of blood donors for their reactivity against Plasmodium falciparum antigens as well as for their functional inhibitory potential; (2) the antibody isolation by either the immortalization of B-cells via transformation with Epstein-Barr virus, or the construction of a phage display library and subsequent panning process; (3) the rescue of antibody genes by RT-PCR; (4) the recombinant production of human monoclonal antibodies and recombinant fragments thereof in heterologous expression systems and (5) the characterization of the isolated antibodies for binding activity and parasite inhibition.
Based on this platform, both by phage display and B-cell transformation, antibodies specific for merozoite surface antigens have been isolated and characterized for their inhibitory potential.
The presented Antibody Isolation Technology Platform allows the ongoing rescue, recombinant production and characterization of multiple human monoclonal antibodies against Plasmodium falciparum antigens and can be flexibly extended by including further donor material. In the future, this technology might allow to rescue and characterize whole specific antibody repertoires.
The human monoclonal antibodies derived from this platform do not only inherit a great potential as a tool for basic and applied research in malariology but also might deliver alternatives for malaria therapy for multi resistant strains. In a further aspect, these antibodies might be suitable as travelers’ vaccines conferring immediate protection.