title: Phase 1 safety and immunogenicity trial of the Plasmodium falciparum blood-stage malaria vaccine AMA1-C1/ISA 720 in Australian adults.
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.
authors.affiliation: Malaria Vaccine Development Branch (MVDB), National Institute of Allergy and Infectious Disease, National Institutes of Health (NIAID/NIH), Rockville, MD, United States.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Pierce
authors.affiliation: Malaria Vaccine Development Branch (MVDB), National Institute of Allergy and Infectious Disease, National Institutes of Health (NIAID/NIH), Rockville, MD, United States. Electronic address: ellisru@niaid.nih.gov.
authors.forename: Ruth D
authors.initials: RD
authors.lastname: Ellis
authors.affiliation: Malaria Vaccine Development Branch (MVDB), National Institute of Allergy and Infectious Disease, National Institutes of Health (NIAID/NIH), Rockville, MD, United States.
authors.forename: Laura B
authors.initials: LB
authors.lastname: Martin
authors.affiliation: PATH Malaria Vaccine Initiative, Bethesda, MD, United States.
authors.forename: Elissa
authors.initials: E
authors.lastname: Malkin
authors.affiliation: PATH Malaria Vaccine Initiative, Bethesda, MD, United States.
authors.forename: Eveline
authors.initials: E
authors.lastname: Tierney
authors.affiliation: Malaria Vaccine Development Branch (MVDB), National Institute of Allergy and Infectious Disease, National Institutes of Health (NIAID/NIH), Rockville, MD, United States.
authors.forename: Kazutoyo
authors.initials: K
authors.lastname: Miura
authors.affiliation: Biostatistics Research Branch, NIAID/NIH, Rockville, MD, United States.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Fay
authors.affiliation: Q-Pharm Pty Ltd, Brisbane, Australia.
authors.forename: Joanne
authors.initials: J
authors.lastname: Marjason
authors.affiliation: Q-Pharm Pty Ltd, Brisbane, Australia.
authors.forename: Suzanne L
authors.initials: SL
authors.lastname: Elliott
authors.affiliation: Malaria Vaccine Development Branch (MVDB), National Institute of Allergy and Infectious Disease, National Institutes of Health (NIAID/NIH), Rockville, MD, United States.
authors.forename: Gregory E D
authors.initials: GED
authors.lastname: Mullen
authors.affiliation: Malaria Vaccine Development Branch (MVDB), National Institute of Allergy and Infectious Disease, National Institutes of Health (NIAID/NIH), Rockville, MD, United States.
authors.forename: Kelly
authors.initials: K
authors.lastname: Rausch
authors.affiliation: Malaria Vaccine Development Branch (MVDB), National Institute of Allergy and Infectious Disease, National Institutes of Health (NIAID/NIH), Rockville, MD, United States.
authors.forename: Daming
authors.initials: D
authors.lastname: Zhu
authors.affiliation: Laboratory of Malaria and Vector Research, NIAID/NIH, Rockville, MD, United States.
authors.forename: Carole A
authors.initials: CA
authors.lastname: Long
authors.affiliation: Malaria Vaccine Development Branch (MVDB), National Institute of Allergy and Infectious Disease, National Institutes of Health (NIAID/NIH), Rockville, MD, United States.
authors.forename: Louis H
authors.initials: LH
authors.lastname: Miller
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000009:adverse effects*; D000293:Adolescent; D000328:Adult; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D000953:Antigens, Protozoan / Q000008:administration & dosage / Q000276:immunology*; D001315:Australia; D004306:Dose-Response Relationship, Immunologic; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006801:Humans; D007117:Immunization, Secondary / Q000379:methods; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D016778:Malaria, Falciparum / Q000276:immunology* / Q000517:prevention & control; D008297:Male; D008353:Mannitol / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D008565:Membrane Proteins / Q000008:administration & dosage / Q000276:immunology*; D008875:Middle Aged; D009829:Oleic Acids / Q000008:administration & dosage / Q000009:adverse effects*; D010963:Plasmodium falciparum / Q000276:immunology*; D015800:Protozoan Proteins / Q000008:administration & dosage / Q000276:immunology*; D055815:Young Adult
chemical_list: D000276:Adjuvants, Immunologic; D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D017780:Malaria Vaccines; D008565:Membrane Proteins; D009829:Oleic Acids; D015800:Protozoan Proteins; C090077:apical membrane antigen I, Plasmodium; C001681:mannide monooleate; D008353:Mannitol