Anti-apical-membrane-antigen-1 antibody is more effective than anti-42-kilodalton-merozoite-surface-protein-1 antibody in inhibiting plasmodium falciparum growth, as determined by the in vitro growth inhibition assay.
Apical membrane antigen 1 (AMA1) and the 42-kDa merozoite surface protein 1 (MSP1(42)) are leading malaria vaccine candidates. Several preclinical and clinical trials have been conducted, and an in vitro parasite growth inhibition assay has been used to evaluate the biological activities of the resulting antibodies. In a U.S. phase 1 trial with AMA1-C1/Alhydrogel plus CPG 7909, the vaccination elicited anti-AMA1 immunoglobulin G (IgG) which showed up to 96% inhibition. However, antibodies induced by MSP1(42)-C1/Alhydrogel plus CPG 7909 vaccine showed less than 32% inhibition in vitro. To determine whether anti-MSP1(42) IgG had less growth-inhibitory activity than anti-AMA1 IgG in vitro, the amounts of IgG that produced 50% inhibition of parasite growth (Ab(50)) were compared for rabbit and human antibodies. The Ab(50)s of rabbit and human anti-MSP1(42) IgGs were significantly higher (0.21 and 0.62 mg/ml, respectively) than those of anti-AMA1 IgGs (0.07 and 0.10 mg/ml, respectively) against 3D7 parasites. Ab(50) data against FVO parasites also demonstrated significant differences. We further investigated the Ab(50)s of mouse and monkey anti-AMA1 IgGs and showed that there were significant differences between the species (mouse, 0.28 mg/ml, and monkey, 0.14 mg/ml, against 3D7 parasites). Although it is unknown whether growth-inhibitory activity in vitro reflects protective immunity in vivo, this study showed that the Ab(50) varies with both antigen and species. Our data provide a benchmark for antibody levels for future AMA1- or MSP1(42)-based vaccine development efforts in preclinical and clinical trials.
Malaria Vaccine Development Branch, National Institute of Allergy and Infectious Diseases, NIH, Rockville, MD 20852, USA. kmiura@niaid.nih.gov
Kazutoyo
K
Miura
Hong
H
Zhou
Ababacar
A
Diouf
Samuel E
SE
Moretz
Michael P
MP
Fay
Louis H
LH
Miller
Laura B
LB
Martin
Mark A
MA
Pierce
Ruth D
RD
Ellis
Gregory E D
GE
Mullen
Carole A
CA
Long
D000328:Adult; D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology* / Q000494:pharmacology; D000953:Antigens, Protozoan / Q000276:immunology*; D000962:Antimalarials / Q000494:pharmacology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D008253:Macaca mulatta; D017780:Malaria Vaccines / Q000276:immunology*; D008565:Membrane Proteins / Q000276:immunology*; D020066:Merozoite Surface Protein 1 / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010963:Plasmodium falciparum / Q000187:drug effects / Q000254:growth & development* / Q000276:immunology*; D015800:Protozoan Proteins / Q000276:immunology*; D011817:Rabbits
D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D000962:Antimalarials; D007074:Immunoglobulin G; D017780:Malaria Vaccines; D008565:Membrane Proteins; D020066:Merozoite Surface Protein 1; D015800:Protozoan Proteins; C090077:apical membrane antigen I, Plasmodium