1. Phase 1 safety and immunogenicity trial of the Plasmodium falciparum blood-stage malaria vaccine AMA1-C1/ISA 720 in Australian adults.
- Author
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Pierce MA, Ellis RD, Martin LB, Malkin E, Tierney E, Miura K, Fay MP, Marjason J, Elliott SL, Mullen GED, Rausch K, Zhu D, Long CA, and Miller LH
- Subjects
- Adjuvants, Immunologic administration & dosage, Adolescent, Adult, Animals, Antibodies, Protozoan blood, Antigens, Protozoan administration & dosage, Australia, Dose-Response Relationship, Immunologic, Drug-Related Side Effects and Adverse Reactions, Female, Humans, Immunization, Secondary methods, Malaria Vaccines administration & dosage, Malaria, Falciparum prevention & control, Male, Mannitol administration & dosage, Mannitol adverse effects, Membrane Proteins administration & dosage, Middle Aged, Oleic Acids administration & dosage, Protozoan Proteins administration & dosage, Young Adult, Adjuvants, Immunologic adverse effects, Antigens, Protozoan immunology, Malaria Vaccines adverse effects, Malaria Vaccines immunology, Malaria, Falciparum immunology, Mannitol analogs & derivatives, Membrane Proteins immunology, Oleic Acids adverse effects, Plasmodium falciparum immunology, Protozoan Proteins immunology
- Abstract
A Phase 1 trial was conducted in malaria-naïve adults to evaluate the recombinant protein vaccine apical membrane antigen 1-Combination 1 (AMA1-C1) formulated in Montanide ISA 720 (SEPPIC, France), a water-in-oil adjuvant. Vaccinations were halted early due to a formulation issue unrelated to stability or potency. Twenty-four subjects (12 in each group) were enrolled and received 5 or 20 microg protein at 0 and 3 months and four subjects were enrolled and received one vaccination of 80 microg protein. After first vaccination, nearly all subjects experienced mild to moderate local reactions and six experienced delayed local reactions occurring at Day 9 or later. After the second vaccination, three subjects experienced transient grade 3 (severe) local reactions; the remainder experienced grade 1 or 2 local reactions. All related systemic reactogenicity was grade 1 or 2, except one instance of grade 3 malaise. Anti-AMA1-C1 antibody responses were dose dependent and seen following each vaccination, with mean antibody levels 2-3 fold higher in the 20 microg group compared to the 5 microg group at most time points. In vitro growth-inhibitory activity was a function of the anti-AMA1 antibody titer. AMA1-C1 formulated in ISA 720 is immunogenic in malaria-naïve Australian adults. It is reasonably tolerated, though some transient, severe, and late local reactions are seen., (Published by Elsevier Ltd.)
- Published
- 2010
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