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|Title: ||Holistic approach to malaria elimination|
|Authors: ||Boes, Alexander|
|Issue Date: ||2013|
|Publisher: ||German Medical Science GMS Publishing House|
|Citation: ||German Medical Science GMS Publishing House; 2013. Doc13mal01. DOI: 10.3205/13mal01, URN: urn:nbn:de:0183-13mal011|
|Abstract: ||Background: Malaria is a devastating infectious disease caused by parasites of the genus Plasmodium. It affects more than 200 million
people worldwide and causes an estimated 700,000 deaths every year, primarily children in developing countries. Effective vaccines
against malaria are not yet available and anti-malarial drugs are becoming less effective as the parasites develop resistance. In
addition to the disease burden malaria has a severe impact on public health and economic welfare, hindering progress in countries
where the disease is endemic. Urgent research is therefore required to holistically address the global burden of malaria.
Approach: Based on the funding of the German Fraunhofer Future Foundation a large multidisciplinary project consortium was formed
to combine expertise from the infection biology, biotechnology, engineering and medical technology fields for the development of
innovative and complementary approaches towards malaria elimination.
Results: We generated novel protein-based multi-stage malaria vaccine candidates against Plasmodium falciparum (Pf) covering antigens
from the pre-erythrocytic, erythrocytic and sexual stages. The vaccine candidates were expressed in yeast (Pichia pastoris) and
plants (Nicotiana benthamiana) and elicited strong, balanced immune responses in mice and rabbits. Binding studies and immunofluorescence
assays demonstrated the native conformation of the vaccine candidates. Affinity-purified pAbs showed strong inhibitory
effects in functional assays for each stage.
In preparation for clinical testing, GMP-compliant production processes are being established for the yeast- and plant-based malaria
vaccine candidates, the latter benefiting from a groundbreaking production facility with integrated vertical farming and 2D/3D-plant
scanners. The facility is under construction at the IME in Aachen and will permit the automated large-scale manufacturing of the malaria
vaccine candidates in plants according to GMP standards as well as the production of certified transgenic seeds.
In addition to the active vaccination, a potential passive vaccination approach against Pf is being explored via a novel technology
platform for the generation of human monoclonal antibodies from peripheral blood mononuclear cells of semi-immune donors. First
inhibitory antibodies have been isolated and are being evaluated.
To complement the therapeutic approach and to strengthen malaria control a novel diagnostic platform for the automated microscopic
acquisition and analysis of Giemsa-stained thin and thick blood smears is being developed. A prototype system has been set up, first
segmentation and classification algorithms were generated and a training database was built including in total images of 4,195 annotated
Pf parasites and 2,881 artifacts. Preliminary evaluation of a non-overlapping test sets provided a detection accuracy rate of 94%
for thick smears and 93% for thin smears, respectively.
Conclusion: The Fraunhofer Future Foundation Malaria Project has introduced a holistic concept to support the elimination of malaria
by focusing not only on the generation of innovative malaria vaccine candidates but also on GMP-compliant process development,
novel enabling technologies for manufacturing and accurate, automated malaria diagnostics.|
|Description: ||An article published by German Medical Science
GMS Publishing House and also available at DOI: 10.3205/13mal01, URN: urn:nbn:de:0183-13mal011|
|Appears in Collections:||College of Health Sciences|
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