Clinical and Vaccine Immunology, July 2009, p. 963-968, Vol. 16, No. 7
1071-412X/09/$08.00+0 doi:10.1128/CVI.00042-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
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
Kazutoyo Miura,1*
Hong Zhou,2
Ababacar Diouf,2
Samuel E. Moretz,2
Michael P. Fay,3
Louis H. Miller,1
Laura B. Martin,1,
Mark A. Pierce,1,
Ruth D. Ellis,1
Gregory E. D. Mullen,1,
and
Carole A. Long2*
Malaria Vaccine Development Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 5640 Fishers Lane, Twinbrook 1, Rockville, Maryland 20852,1 Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 12735 Twinbrook Parkway, Twinbrook 3, Rockville, Maryland 20852,2 Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 6700A Rockledge Drive, Bethesda, Maryland 208173
Received 27 January 2009/ Returned for modification 7 April 2009/ Accepted 6 May 2009
Apical membrane antigen 1 (AMA1) and the 42-kDa merozoite surface protein 1 (MSP142) 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 MSP142-C1/Alhydrogel plus CPG 7909 vaccine showed less than 32% inhibition in vitro. To determine whether anti-MSP142 IgG had less growth-inhibitory activity than anti-AMA1 IgG in vitro, the amounts of IgG that produced 50% inhibition of parasite growth (Ab50) were compared for rabbit and human antibodies. The Ab50s of rabbit and human anti-MSP142 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. Ab50 data against FVO parasites also demonstrated significant differences. We further investigated the Ab50s 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 Ab50 varies with both antigen and species. Our data provide a benchmark for antibody levels for future AMA1- or MSP142-based vaccine development efforts in preclinical and clinical trials.
* Corresponding author. Mailing address for Kazutoyo Miura: 12441 Parklawn Drive, Twinbrook 2, Room 107, Rockville, MD 20852. Phone: (301) 435-2176. Fax: (301) 443-5778. E-mail: kmiura{at}niaid.nih.gov. Mailing address for Carole A. Long: 12735 Twinbrook Parkway, Twinbrook 3, Room 3W-13, Rockville, MD 20852. Phone: (301) 496-3655. Fax: (301) 443-5778. E-mail: clong{at}niaid.nih.gov
Published ahead of print on 13 May 2009.
Present address: Novartis Vaccines Institute for Global Health, Siena, Italy.
Present address: Cookeville Regional Medical Center, 1 Medical Center Drive, Cookeville, TN 38506.
Present address: Division of Imaging Sciences, King's College London, The Rayne Institute, Thomas' Hospital, London, United Kingdom.
Clinical and Vaccine Immunology, July 2009, p. 963-968, Vol. 16, No. 7
1071-412X/09/$08.00+0 doi:10.1128/CVI.00042-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
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