Experimental infection and protection against ... - TI Pharma
Experimental infection and protection against ... - TI Pharma Experimental infection and protection against ... - TI Pharma
Safety and Immunogenicity of a Recombinant Plasmodium falciparum AMA1 Malaria vaccine Adjuvanted with Alhydrogel TM, Montanide ISA 720 or AS02 Figure 5. Stimulation indices in response to 6 µg/ml PfAMA1 presented as box plots and whiskers. Peripheral Blood Mononuclear Cells from immunised volunteers 28 days after the second immunisation and 28 days after the third immunisation (Day 56 and 84 respectively) were stimulated with 6 µg of PfAMA1 vaccine. Cell proliferation was measured by adding 3H thymidine and calculated relative to control wells. Box plots and whiskers show the range and the 25th, 50th and 75th percentile. Circles represent outliers. Measurements were performed at baseline, 28 days after the second immunisation and 28 days after the third immunisation (day 56 and 84 respectively). Sera from vaccinees could be shown to recognise the native PfAMA1 by immunofluorescence in a dose dependent manner. Eight of fifteen samples were positive in IFA, amongst which were four samples with the highest antibody titres. The staining pattern found in positive samples localised to the same structures as 4G2 rat monoclonal antibody (Figure 3). Cellular immune response In all groups, induction of IFNγ and IL-5 cytokines could be demonstrated (Figure 4). The magnitude of cytokine production was not dose dependent or depen- 47
48 Chapter 2 Figure 6. Percentage of growth inhibition of FVO-strain P. falciparum parasites after addition of 5 or 10 mg/ml IgG. Serum samples from volunteers immunised with PfAMA1 were obtained four weeks after the final immunisation by per protocol analysis and included in a merozoite growth inhibition assay. Growth inhibition is expressed as a percentage to control. Boxes show 25th, 50th and 75th percentile growth inhibition, whiskers show the range, circles are outliers. dent on the number of immunisations. Rather, IFNγ production in many samples decreased after the third immunisation. For both cytokines, PfAMA1 induction was comparable or higher than that following stimulation with 5 µg Tetanus Toxoid (data not shown). Cytokine production in the different groups did not differ significantly from each other (for IFNγ p = 0.18, for IL-5 p = 0.14). Ratio’s of IFNγ / IL-5 production were also not significantly different between adjuvant groups (data not shown), but showed a trend towards higher ratio in the Montanide and AS02 groups (Day 84 mean ratio Alhydrogel: 1.16 (95% CI: 0.08 to 2.23), Montanide: 2.82 (95% CI: 1.44 to 4.21), AS02: 2.66 (95% CI: 0.57 to 4.76)). All groups showed Peripheral Blood Mononuclear Cell proliferation upon stimulation with PfAMA1 (Figure 5). Stimulation indices between PBMC’s stimulated with 30, 6 or 1.2 µg/ml PfAMA1 were similar. All groups of volunteers
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- Page 6: Contents Contents 5 Chapter 1 - Int
- Page 10 and 11: Introduction 9 Malaria Malaria is o
- Page 12 and 13: Introduction 11 Preclinical Clinica
- Page 14 and 15: Introduction 13 pipeline of clinica
- Page 16 and 17: Introduction 15 The division of ant
- Page 18 and 19: Introduction 17 Figure 4. Populatio
- Page 20 and 21: Introduction 19 candidates. Initial
- Page 22 and 23: Introduction 21 - to identify param
- Page 24 and 25: Introduction 23 20. Nussenzweig RS,
- Page 26 and 27: Introduction 25 50. Ouedraogo AL, R
- Page 28: Introduction 27 RTS,S/AS02 in malar
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- Page 58 and 59: Chapter 3 Humoral immune responses
- Page 60 and 61: Humoral immune responses to a singl
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- Page 91 and 92: 90 Chapter 4 positively correlated
- Page 93 and 94: 92 Chapter 4 Acknowledgements The a
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48 Chapter 2<br />
Figure 6. Percentage of growth inhibition of FVO-strain P. falciparum<br />
parasites after addition of 5 or 10 mg/ml IgG. Serum samples from volunteers<br />
immunised with PfAMA1 were obtained four weeks after the final<br />
immunisation by per protocol analysis <strong>and</strong> included in a merozoite growth<br />
inhibition assay. Growth inhibition is expressed as a percentage to control.<br />
Boxes show 25th, 50th <strong>and</strong> 75th percentile growth inhibition, whiskers show<br />
the range, circles are outliers.<br />
dent on the number of immunisations. Rather, IFNγ production in many samples<br />
decreased after the third immunisation. For both cytokines, PfAMA1 induction<br />
was comparable or higher than that following stimulation with 5 µg Tetanus<br />
Toxoid (data not shown). Cytokine production in the different groups did not<br />
differ significantly from each other (for IFNγ p = 0.18, for IL-5 p = 0.14). Ratio’s of<br />
IFNγ / IL-5 production were also not significantly different between adjuvant<br />
groups (data not shown), but showed a trend towards higher ratio in the<br />
Montanide <strong>and</strong> AS02 groups (Day 84 mean ratio Alhydrogel: 1.16 (95% CI: 0.08<br />
to 2.23), Montanide: 2.82 (95% CI: 1.44 to 4.21), AS02: 2.66 (95% CI: 0.57 to<br />
4.76)).<br />
All groups showed Peripheral Blood Mononuclear Cell proliferation upon<br />
stimulation with PfAMA1 (Figure 5). Stimulation indices between PBMC’s<br />
stimulated with 30, 6 or 1.2 µg/ml PfAMA1 were similar. All groups of volunteers
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