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

• Published in: PloS one Vol. 3; no. 12; p. e3960
• Main 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 HM, Arnold, Miranda, Walraven, Vanessa, Teelen, Karina, Roeffen, Will, de Mast, Quirijn, Ballou, WRipley, Cohen, Joe, Dubois, Marie Claude, Ascarateil, Stephane, van der Ven, Andre, Thomas, Alan, Sauerwein, Robert, Beeson, James G
• Format: Journal Article
• Language: English
• Published: 01.01.2008
• Subjects: Pichia pastoris; Plasmodium falciparum
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0003960

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 mu g and 50 mu g doses with three different adjuvants, Alhydrogel registered , 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 mu g 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50 mm) were withdrawn as they met the stopping criteria.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 IFN gamma 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 <ext-link ext-link-type="uri" xlink:href="http://www.clinicaltrials.gov/ct2/show/NCT00730782?ter m NCT00730782&rank1">NCT00730782