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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

The relation between GIA and IgG titre.The IC50 value is indicated by red lines. The various colours represent the time points at which samples were taken: day 42 dark blue, day 70 orange, day 91 light blue, day 202 green, day 217 purple and day 252 red.
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pone-0020547-g007: The relation between GIA and IgG titre.The IC50 value is indicated by red lines. The various colours represent the time points at which samples were taken: day 42 dark blue, day 70 orange, day 91 light blue, day 202 green, day 217 purple and day 252 red.

Mentions: The relation between IgG and GIA was investigated by modeling a sigmoid curve using non-linear least squares regression. Day 0 samples from both groups were included and PkAMA1 vaccinated animals were used for time points thereafter. Analysis was restricted to GIA values from one GIA run at 10 mg mL−1 IgG, which corresponds to the amount of total IgG present in rhesus serum (days 42, 70, 91, 202, 217 and 252). Thus the amounts of GIA and PkAMA1-specific IgG both correspond to values obtained with undiluted serum or plasma. The relationship between GIA and PkAMA1-specific IgG is graphically presented in figure 7. The correlation coefficient was 0.908 (95% CI 0.841 to 0.948, p<0.0001). The IC50 value was estimated at 38 kAU mL−1 P. knowlesi AMA1-specific IgG (95% CI 31 to 46) and the fold difference in IgG between 10 and 90% GIA was estimated at 15.4 fold (95% CI 7.8 to 59.5) (Figure 7).


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)

The relation between GIA and IgG titre.The IC50 value is indicated by red lines. The various colours represent the time points at which samples were taken: day 42 dark blue, day 70 orange, day 91 light blue, day 202 green, day 217 purple and day 252 red.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0020547-g007: The relation between GIA and IgG titre.The IC50 value is indicated by red lines. The various colours represent the time points at which samples were taken: day 42 dark blue, day 70 orange, day 91 light blue, day 202 green, day 217 purple and day 252 red.
Mentions: The relation between IgG and GIA was investigated by modeling a sigmoid curve using non-linear least squares regression. Day 0 samples from both groups were included and PkAMA1 vaccinated animals were used for time points thereafter. Analysis was restricted to GIA values from one GIA run at 10 mg mL−1 IgG, which corresponds to the amount of total IgG present in rhesus serum (days 42, 70, 91, 202, 217 and 252). Thus the amounts of GIA and PkAMA1-specific IgG both correspond to values obtained with undiluted serum or plasma. The relationship between GIA and PkAMA1-specific IgG is graphically presented in figure 7. The correlation coefficient was 0.908 (95% CI 0.841 to 0.948, p<0.0001). The IC50 value was estimated at 38 kAU mL−1 P. knowlesi AMA1-specific IgG (95% CI 31 to 46) and the fold difference in IgG between 10 and 90% GIA was estimated at 15.4 fold (95% CI 7.8 to 59.5) (Figure 7).

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