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Vaccination with Plasmodium knowlesi AMA1 formulated in the novel adjuvant co-vaccine HT™ protects against blood-stage challenge in rhesus macaques.

Mahdi Abdel Hamid M, Remarque EJ, van Duivenvoorde LM, van der Werff N, Walraven V, Faber BW, Kocken CH, Thomas AW - PLoS ONE (2011)

Bottom Line: 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.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.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 IC(50) values correlated with estimated in vivo growth rates.

View Article: PubMed Central - PubMed

Affiliation: Department of Parasitology, Biomedical Primate Research Centre, Rijswijk, The Netherlands.

ABSTRACT
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 IC(50) values correlated with estimated in vivo growth rates.

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Related in: MedlinePlus

Study schedule.Timing of immunisations and challenges.
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pone-0020547-g001: Study schedule.Timing of immunisations and challenges.

Mentions: 12 healthy adult rhesus macaques weighing between 5 to 13 kg, were selected for the study. The animals were all shown to be negative for Plasmodium parasites, anti-PfAMA1 or anti-PkAMA1 antibodies. Animals were stratified over two groups of six animals, with similar characteristics with respect to sex, age, and weight. Treatments were then randomly assigned (Table 1). All vaccinations and venapunctures were performed on ketamine-sedated animals. Monkeys in the experimental group (N = 6) were immunised with 50 µg PkAMA1 DI-II-III (aa43–487) formulated in CoVaccine HT™ and the control monkeys (N = 6) were immunised with 50 µg GMP-grade PfAMA1 FVO strain DI-II-III (aa25–545) formulated in CoVaccine HT™. Vaccines were given intramuscularly in alternating upper legs on days 0, 28 and 56. Animals were bled before each immunisation and on days 1, 7, and 14 following each vaccination. After the primary parasite challenge animals were left to recover before a 50 µg booster dose of Pk or PfAMA1 was given on day 203 and animals were re-challenged two weeks later (day 217). The follow up was 35 days. Monkeys were left to recover from the second challenge and were boosted with 50 µg Pk or PfAMA1 on day 435, and challenged again on day 450. Follow up time was 34 days (Figure 1).


Vaccination with Plasmodium knowlesi AMA1 formulated in the novel adjuvant co-vaccine HT™ protects against blood-stage challenge in rhesus macaques.

Mahdi Abdel Hamid M, Remarque EJ, van Duivenvoorde LM, van der Werff N, Walraven V, Faber BW, Kocken CH, Thomas AW - PLoS ONE (2011)

Study schedule.Timing of immunisations and challenges.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3105089&req=5

pone-0020547-g001: Study schedule.Timing of immunisations and challenges.
Mentions: 12 healthy adult rhesus macaques weighing between 5 to 13 kg, were selected for the study. The animals were all shown to be negative for Plasmodium parasites, anti-PfAMA1 or anti-PkAMA1 antibodies. Animals were stratified over two groups of six animals, with similar characteristics with respect to sex, age, and weight. Treatments were then randomly assigned (Table 1). All vaccinations and venapunctures were performed on ketamine-sedated animals. Monkeys in the experimental group (N = 6) were immunised with 50 µg PkAMA1 DI-II-III (aa43–487) formulated in CoVaccine HT™ and the control monkeys (N = 6) were immunised with 50 µg GMP-grade PfAMA1 FVO strain DI-II-III (aa25–545) formulated in CoVaccine HT™. Vaccines were given intramuscularly in alternating upper legs on days 0, 28 and 56. Animals were bled before each immunisation and on days 1, 7, and 14 following each vaccination. After the primary parasite challenge animals were left to recover before a 50 µg booster dose of Pk or PfAMA1 was given on day 203 and animals were re-challenged two weeks later (day 217). The follow up was 35 days. Monkeys were left to recover from the second challenge and were boosted with 50 µg Pk or PfAMA1 on day 435, and challenged again on day 450. Follow up time was 34 days (Figure 1).

Bottom Line: 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.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.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 IC(50) values correlated with estimated in vivo growth rates.

View Article: PubMed Central - PubMed

Affiliation: Department of Parasitology, Biomedical Primate Research Centre, Rijswijk, The Netherlands.

ABSTRACT
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 IC(50) values correlated with estimated in vivo growth rates.

Show MeSH
Related in: MedlinePlus