Phase 1 safety and immunogenicity trial of the Plasmodium falciparum blood-stage malaria vaccine AMA1-C1/ISA 720 in Australian adults.
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.
Pierce
Mark A
MA
Malaria Vaccine Development Branch (MVDB), National Institute of Allergy and Infectious Disease, National Institutes of Health (NIAID/NIH), Rockville, MD, United States.
Ellis
Ruth D
RD
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.
Martin
Laura B
LB
Malaria Vaccine Development Branch (MVDB), National Institute of Allergy and Infectious Disease, National Institutes of Health (NIAID/NIH), Rockville, MD, United States.
Malkin
Elissa
E
PATH Malaria Vaccine Initiative, Bethesda, MD, United States.
Tierney
Eveline
E
PATH Malaria Vaccine Initiative, Bethesda, MD, United States.
Miura
Kazutoyo
K
Malaria Vaccine Development Branch (MVDB), National Institute of Allergy and Infectious Disease, National Institutes of Health (NIAID/NIH), Rockville, MD, United States.
Fay
Michael P
MP
Biostatistics Research Branch, NIAID/NIH, Rockville, MD, United States.
Marjason
Joanne
J
Q-Pharm Pty Ltd, Brisbane, Australia.
Elliott
Suzanne L
SL
Q-Pharm Pty Ltd, Brisbane, Australia.
Mullen
Gregory E D
GED
Malaria Vaccine Development Branch (MVDB), National Institute of Allergy and Infectious Disease, National Institutes of Health (NIAID/NIH), Rockville, MD, United States.
Rausch
Kelly
K
Malaria Vaccine Development Branch (MVDB), National Institute of Allergy and Infectious Disease, National Institutes of Health (NIAID/NIH), Rockville, MD, United States.
Zhu
Daming
D
Malaria Vaccine Development Branch (MVDB), National Institute of Allergy and Infectious Disease, National Institutes of Health (NIAID/NIH), Rockville, MD, United States.
Long
Carole A
CA
Laboratory of Malaria and Vector Research, NIAID/NIH, Rockville, MD, United States.
Miller
Louis H
LH
Malaria Vaccine Development Branch (MVDB), National Institute of Allergy and Infectious Disease, National Institutes of Health (NIAID/NIH), Rockville, MD, United States.
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
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