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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Vaccination with Plasmodium knowlesi AMA1 formulated in the novel adjuvant co-vaccine HT™ protects against blood-stage challenge in rhesus macaques
PLoS ONE, Volume 6, No. 5, Article e20547, Year 2011
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Description
Plasmodium falciparum apical membrane antigen 1 (PfAMA1) is a leading blood stage vaccine candidate. Plasmodium knowlesi AMA1 (PkAMA1) was produced and purified using similar methodology as for clinical grade PfAMA1 yielding a pure, conformational intact protein. Combined with the adjuvant CoVaccine HT™, PkAMA1 was found to be highly immunogenic in rabbits and the efficacy of the PkAMA1 was subsequently tested in a rhesus macaque blood-stage challenge model. Six rhesus monkeys were vaccinated with PkAMA1 and a control group of 6 were vaccinated with PfAMA1. A total of 50 μg AMA1 was administered intramuscularly three times at 4 week intervals. One of six rhesus monkeys vaccinated with PkAMA1 was able to control parasitaemia, upon blood stage challenge with P. knowlesi H-strain. Four out of the remaining five showed a delay in parasite onset that correlated with functional antibody titres. In the PfAMA1 vaccinated control group, five out of six animals had to be treated with antimalarials 8 days after challenge; one animal did not become patent during the challenge period. Following a rest period, animals were boosted and challenged again. Four of the six rhesus monkeys vaccinated with PkAMA1 were able to control the parasitaemia, one had a delayed onset of parasitaemia and one animal was not protected, while all control animals required treatment. To confirm that the control of parasitaemia was AMA1-related, animals were allowed to recover, boosted and re-challenged with P. knowlesi Nuri strain. All control animals had to be treated with antimalarials by day 8, while five out of six PkAMA1 vaccinated animals were able to control parasitaemia. This study shows that: i) Yeast-expressed PkAMA1 can protect against blood stage challenge; ii) Functional antibody levels as measured by GIA correlated inversely with the day of onset and iii) GIA IC50 values correlated with estimated in vivo growth rates. © 2011 Mahdi Abdel Hamid et al.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC3105089/bin/pone.0020547.s001.eps
Authors & Co-Authors
Mahdi Abdel Hamid, Muzamil Mahdi
Netherlands, Rijswijk
Biomedical Primate Research Centre - Rijswijk
Sudan, Khartoum
Institute of Endemic Diseases Sudan
Remarque, Edmond J.
Netherlands, Rijswijk
Biomedical Primate Research Centre - Rijswijk
van Duivenvoorde, Leonie M.
Netherlands, Rijswijk
Biomedical Primate Research Centre - Rijswijk
Netherlands, Amsterdam
Universiteit Van Amsterdam
van der Werff, Nicole M.
Netherlands, Rijswijk
Biomedical Primate Research Centre - Rijswijk
Walraven, Vanessa
Netherlands, Rijswijk
Biomedical Primate Research Centre - Rijswijk
Netherlands, Schiedam
Vlietland Ziekenhuis
Faber, Bart W.
Netherlands, Rijswijk
Biomedical Primate Research Centre - Rijswijk
Kocken, Clemens H.M.
Netherlands, Rijswijk
Biomedical Primate Research Centre - Rijswijk
Thomas, Alan W.
Netherlands, Rijswijk
Biomedical Primate Research Centre - Rijswijk
Statistics
Citations: 67
Authors: 8
Affiliations: 4
Identifiers
Doi:
10.1371/journal.pone.0020547
e-ISSN:
19326203
Study Design
Randomised Control Trial