New route for development of a malaria
vaccine
November 2008
Researchers from Radboud University Nijmegen Medical Centre,
Nijmegen, the Netherlands and LUMC, Leiden, the Netherlands have
discovered a potential new route for genetically modifying the malaria
parasite and developing a new malaria vaccine.
Every day 2000 children die from malaria in Africa alone. The
infection is transmitted from human to human by biting mosquitoes and
remains one of the world’s most devastating diseases. Despite many years
of effort a vaccine is still not available but is urgently needed, if we
are to make an impact on this enormous problem.
Continual exposure can generate protection against malaria and can be
acquired through an exposure to a high number of infectious mosquito
bites. Parasites that are injected by a mosquito first migrate to the
liver where they mature and then are released into the blood circulation
and it is only here that they cause disease and fatal complications.
A very promising method for vaccination is to sufficiently weaken
parasites such that they invade liver cells but then are not able to
develop any further. It is, however, required that these attenuated
parasites are still able to stimulate a good immune response in the
liver. This can be achieved by irradiating the parasites or by
genetically inactivating individual parasite genes that are active
during the parasites growth in the liver.
Researchers from Radboud University Nijmegen Medical Centre,
Nijmegen, the Netherlands and LUMC, Leiden, the Netherlands, have now
characterized a large number of parasite proteins (‘proteome’) that are
present only during liver stage development and therefore are potential
targets for inactivation.
The research groups had previously shown that protection in mice can
be achieved by vaccinating mice with a rodent malaria which had one of
these liver stage genes removed, specifically p36p. Moreover, the
protection was long lasting and virtually complete.
Now, these same researchers from Nijmegen and Leiden have succeeded
in making the first critical transition from the rodent system to humans
by inactivating the equivalent gene (p52) in the most important human
malaria parasite, P. falciparum. Similar to the results with the
rodent parasite, these human parasites are unable to develop in liver
cells. This is the first time that genetic modification of a human
parasite results in its growth arrest in a liver cell, opening up
exciting possibilities for its use as a human vaccine.
These studies form part of a collaborative project with the American
company Sanaria, whose sole purpose is develop a whole organism malaria
parasite vaccine for use in humans, and is funded by TI-Pharma. These
studies show how results obtained in rodent models of malaria can be
pipelined to form the basis for clinical development of anti-malaria
vaccines in humans.
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