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- Title
Safety and Immunogenicity of a Recombinant Plasmodium falciparum AMA1 Malaria Vaccine Adjuvanted with Alhydrogel, Montanide ISA 720 or AS02.
- Authors
Roestenberg, Meta; Remarque, Ed; de Jonge, Erik; Hermsen, Rob; Blythman, Hildur; Leroy, Odile; Imoukhuede, Egeruan; Jepsen, Soren; Ofori-Anyinam, Opokua; Faber, Bart; Kocken, Clemens H. M.; Arnold, Miranda; Walraven, Vanessa; Teelen, Karina; Roeffen, Will; de Mast, Quirijn; Ballou, W. Ripley; Cohen, Joe; Dubois, Marie Claude; Ascarateil, Stéphane
- 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 doseescalating, phase Ia trial. PfAMA1 FVO strain, produced in Pichia pastoris, was reconstituted at 10 mg 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 mg 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dose, six volunteers in the AS02 group and one in the Montanide group who reported grade 3 erythema (.50 mm) were withdrawn as they met the stopping criteria.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 IFNc and IL-5 cytokines. Conclusions/Significance: All formulations showed distinct reactogenicity profiles. All formulations with PfAMA1 were immunogenic and induced functional antibodies.
- Subjects
PLASMODIUM falciparum; MALARIA vaccines; ANTIGENS; IMMUNOGLOBULINS; PROTOZOAN vaccines; ERYTHROCYTES; IMMUNOLOGICAL adjuvants; VOLUNTEERS; CYTOKINES
- Publication
PLoS ONE, 2008, Vol 3, Issue 12, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0003960