Vaccination with Plasmodium knowlesi AMA1 Formulated in the Novel Adjuvant Co-Vaccine HTTM Protects against Blood-Stage Challenge in Rhesus Macaques

dc.FacultyEndemic Diseasesen_US
dc.contributor.authorAbdel Hamid, Muzamil M.
dc.contributor.authorJ. Remarque, Edmond
dc.contributor.authorM. van Duivenvoorde, Leonie
dc.contributor.authorder Werff, Nicole van
dc.contributor.editorDenise L. Doolan, Queensland Institute of Medical Research, Australiaen_US
dc.contributor.otherParasitologyen_US
dc.date2011
dc.date.accessioned2015-11-12T06:56:42Z
dc.date.available2015-11-12T06:56:42Z
dc.date.issued2015-11-12
dc.date.submitted2015
dc.description.abstractPlasmodium 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 HTTM, 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 mg 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.en_US
dc.identifier.urihttp://khartoumspace.uofk.edu/123456789/16995
dc.publisheruniversity of khartoumen_US
dc.subjectVaccination with Plasmodium knowlesi AMA1 Formulated in the Novel Adjuvant Co-Vaccine HTTM Protects against Blood-Stage Challenge in Rhesus Macaquesen_US
dc.titleVaccination with Plasmodium knowlesi AMA1 Formulated in the Novel Adjuvant Co-Vaccine HTTM Protects against Blood-Stage Challenge in Rhesus Macaquesen_US
dc.typePublicationen_US

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