S B Sirima1, C Durier2, L Kara3, S Houard4, A Gansane1, P Loulergue3, M Bahuaud5, N Benhamouda6, I Nebié1, B Faber7, E Remarque7, O Launay8. 1. Centre National de Recherche et de Formation sur le Paludisme (CNRFP), Ouagadougou, Burkina Faso. 2. INSERM SC10-US19, Villejuif, France. 3. INSERM CIC 1417, F-CRIN, I-REIVAC, Paris, France; Assistance Publique -Hôpitaux de Paris (AP HP), Hôpital Cochin, CIC Cochin-Pasteur, Paris, France. 4. European Vaccine Initiative (EVI), Heidelberg, Germany. 5. AP HP, Hôpital Cochin, Plateforme d'immuno-monitoring vaccinal, Laboratoire d'Immunologie, Paris, France. 6. INSERM U970, Paris, France; AP-HP, Hôpital Européen Georges Pompidou, Service d'Immunologie Biologique, Paris, France. 7. Department of Parasitology, Biomedical Primate Research Centre, Rijswijk, The Netherlands. 8. INSERM CIC 1417, F-CRIN, I-REIVAC, Paris, France; Assistance Publique -Hôpitaux de Paris (AP HP), Hôpital Cochin, CIC Cochin-Pasteur, Paris, France; Université Paris Descartes; Sorbonne Paris-Cité, Paris, France. Electronic address: odile.launay@aphp.fr.
Abstract
BACKGROUND:Plasmodium falciparum Apical Membrane Antigen 1 Diversity Covering (PfAMA1-DiCo) candidate vaccine is a formulation of three recombinant variants of AMA1 designed to provide broader protection against parasites with varying AMA1 sequences. METHODS: In this staggered phase Ia/Ib randomized, double blind trial, healthy French adults received AMA1-DiCo with either Alhydrogel® (n=15) or GLA-SE (n=15). Following a safety assessment in French volunteers, GLA-SE was chosen for the phase Ib trial where healthy Burkinabe adults received either AMA1-DiCo/GLA-SE (n=18) or placebo (n=18). AMA1-DiCo (50µg) was administered intramuscularly at baseline, Week 4 and 26. RESULTS: AMAI-DiCo was safe, well tolerated either with Alhydrogel® or GLA-SE. In European volunteers, the ratios of IgG increase from baseline were about 100 fold in Alhydrogel® group and 200-300 fold in GLA-SE group for the three antigens. In African volunteers, immunization resulted in IgG levels exceeding those observed for the European volunteers with a 4-fold increase. DiCo-specific IgG remained higher 26weeks after the third immunization than at baseline in both European and African volunteers. Induced antibodies were reactive against whole parasite derived from different strains. CONCLUSION:AMA1-DiCo vaccine was safe and immunogenic whatever the adjuvant although GLA-SE appeared more potent than Alhydrogel® at inducing IgG responses. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov NCT02014727; PACTR201402000719423.
RCT Entities:
BACKGROUND:Plasmodium falciparum Apical Membrane Antigen 1 Diversity Covering (PfAMA1-DiCo) candidate vaccine is a formulation of three recombinant variants of AMA1 designed to provide broader protection against parasites with varying AMA1 sequences. METHODS: In this staggered phase Ia/Ib randomized, double blind trial, healthy French adults received AMA1-DiCo with either Alhydrogel® (n=15) or GLA-SE (n=15). Following a safety assessment in French volunteers, GLA-SE was chosen for the phase Ib trial where healthy Burkinabe adults received either AMA1-DiCo/GLA-SE (n=18) or placebo (n=18). AMA1-DiCo (50µg) was administered intramuscularly at baseline, Week 4 and 26. RESULTS: AMAI-DiCo was safe, well tolerated either with Alhydrogel® or GLA-SE. In European volunteers, the ratios of IgG increase from baseline were about 100 fold in Alhydrogel® group and 200-300 fold in GLA-SE group for the three antigens. In African volunteers, immunization resulted in IgG levels exceeding those observed for the European volunteers with a 4-fold increase. DiCo-specific IgG remained higher 26weeks after the third immunization than at baseline in both European and African volunteers. Induced antibodies were reactive against whole parasite derived from different strains. CONCLUSION: AMA1-DiCo vaccine was safe and immunogenic whatever the adjuvant although GLA-SE appeared more potent than Alhydrogel® at inducing IgG responses. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov NCT02014727; PACTR201402000719423.
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