Details

Autor(en) / Beteiligte

• Duncan, Christopher J A
• Sheehy, Susanne H
• Ewer, Katie J
• Douglas, Alexander D
• Collins, Katharine A
• Halstead, Fenella D
• Elias, Sean C
• Lillie, Patrick J
• Rausch, Kelly
• Aebig, Joan
• Miura, Kazutoyo
• Edwards, Nick J
• Poulton, Ian D
• Hunt-Cooke, Angela
• Porter, David W
• Thompson, Fiona M
• Rowland, Ros
• Draper, Simon J
• Gilbert, Sarah C
• Fay, Michael P
• Long, Carole A
• Zhu, Daming
• Wu, Yimin
• Martin, Laura B
• Anderson, Charles F
• Lawrie, Alison M
• Hill, Adrian V S
• Ellis, Ruth D
• Gregson, Aric

Titel

Impact on malaria parasite multiplication rates in infected volunteers of the protein-in-adjuvant vaccine AMA1-C1/Alhydrogel+CPG 7909

Ist Teil von

• PloS one, 2011-07, Vol.6 (7), p.e22271

Ort / Verlag

United States: Public Library of Science

Erscheinungsjahr

2011

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Inhibition of parasite growth is a major objective of blood-stage malaria vaccines. The in vitro assay of parasite growth inhibitory activity (GIA) is widely used as a surrogate marker for malaria vaccine efficacy in the down-selection of candidate blood-stage vaccines. Here we report the first study to examine the relationship between in vivo Plasmodium falciparum growth rates and in vitro GIA in humans experimentally infected with blood-stage malaria. In this phase I/IIa open-label clinical trial five healthy malaria-naive volunteers were immunised with AMA1/C1-Alhydrogel+CPG 7909, and together with three unvaccinated controls were challenged by intravenous inoculation of P. falciparum infected erythrocytes. A significant correlation was observed between parasite multiplication rate in 48 hours (PMR) and both vaccine-induced growth-inhibitory activity (Pearson r = -0.93 [95% CI: -1.0, -0.27] P = 0.02) and AMA1 antibody titres in the vaccine group (Pearson r = -0.93 [95% CI: -0.99, -0.25] P = 0.02). However immunisation failed to reduce overall mean PMR in the vaccine group in comparison to the controls (vaccinee 16 fold [95% CI: 12, 22], control 17 fold [CI: 0, 65] P = 0.70). Therefore no impact on pre-patent period was observed (vaccine group median 8.5 days [range 7.5-9], control group median 9 days [range 7-9]). Despite the first observation in human experimental malaria infection of a significant association between vaccine-induced in vitro growth inhibitory activity and in vivo parasite multiplication rate, this did not translate into any observable clinically relevant vaccine effect in this small group of volunteers. ClinicalTrials.gov [NCT00984763].