Safety and Immunogenicity of a Recombinant Plasmodium falciparum AMA1 Malaria Vaccine Adjuvanted with Alhydrogel™, Montanide ISA 720 or AS02

Meta Roestenberg, Ed Remarque, Erik de Jonge, Rob Hermsen, Hildur Blythman, Odile Leroy, Egeruan Imoukhuede, Soren Jepsen, Opokua Ofori-Anyinam, Bart Faber, Clemens H M Kocken, Miranda Arnold, Vanessa Walraven, Karina Teelen, Will Roeffen, Quirijn de Mast, W Ripley Ballou, Joe Cohen, Marie Claude Dubois, Stéphane Ascarateil, Andre van der Ven, Alan Thomas and Robert Sauerwein

PLOS ONE, 2008, vol. 3, issue 12, 1-12

Abstract: Background: Plasmodium falciparum Apical Membrane Antigen 1 (PfAMA1) is a candidate vaccine antigen expressed by merozoites and sporozoites. It plays a key role in red blood cell and hepatocyte invasion that can be blocked by antibodies. Methodology/Principal Findings: We assessed the safety and immunogenicity of recombinant PfAMA1 in a dose-escalating, phase Ia trial. PfAMA1 FVO strain, produced in Pichia pastoris, was reconstituted at 10 µg and 50 µg doses with three different adjuvants, Alhydrogel™, Montanide ISA720 and AS02 Adjuvant System. Six randomised groups of healthy male volunteers, 8–10 volunteers each, were scheduled to receive three immunisations at 4-week intervals. Safety and immunogenicity data were collected over one year. Transient pain was the predominant injection site reaction (80–100%). Induration occurred in the Montanide 50 µg group, resulting in a sterile abscess in two volunteers. Systemic adverse events occurred mainly in the AS02 groups lasting for 1–2 days. Erythema was observed in 22% of Montanide and 59% of AS02 group volunteers. After the second dose, six volunteers in the AS02 group and one in the Montanide group who reported grade 3 erythema (>50 mm) were withdrawn as they met the stopping criteria. All adverse events resolved. There were no vaccine-related serious adverse events. Humoral responses were highest in the AS02 groups. Antibodies showed activity in an in vitro growth inhibition assay up to 80%. Upon stimulation with the vaccine, peripheral mononuclear cells from all groups proliferated and secreted IFNγ and IL-5 cytokines. Conclusions/Significance: All formulations showed distinct reactogenicity profiles. All formulations with PfAMA1 were immunogenic and induced functional antibodies. Trial Registration: Clinicaltrials.gov NCT00730782

Date: 2008
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Persistent link: https://EconPapers.repec.org/RePEc:plo:pone00:0003960

DOI: 10.1371/journal.pone.0003960

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