|
| |
|
|
|
|
||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | ||||
First published online September 23, 2003
Review Article |
Progress in the development of recombinant and synthetic blood-stage malaria vaccines
Malaria Vaccine Development Unit, NIAID, NIH, Twin Brook I, 5640 Fishers Lane, Rockville, MD 20852, USA
* Author for correspondence (e-mail: smahanty{at}niaid.nih.gov)
Accepted 7 August 2003
The use of asexual blood-stage proteins as malaria vaccines is strongly supported by experimental data directly implicating antibodies induced by these antigens in parasite clearance and protection from re-challenge. The selection of blood-stage antigens is based on their ability to interfere with the pathogenesis of clinical malaria by reducing parasitemias. These vaccines could complement other vaccines aimed at preventing infection, such as those targeted at pre-erythrocytic or mosquito stages of the parasite. Asexual blood-stage vaccines may reduce disease by blockade of red blood cell invasion, inhibition of parasite growth in red cells or interference in cytoadherence of infected red cells. Clearance of blood-stage parasites is dependent primarily on antibody-mediated mechanisms, but CD4 T cells may also play an important role in help for B cells and probably have a direct effector function in the clearance of blood-stage parasites. Since asexual blood-stage parasites reside within erythrocytes, they are accessible to immune clearance mechanisms only for a short time, which imposes special requirements on vaccines. For example, immunity that induces high titers of antibody will be required. Antigenic variation and extensive polymorphism of malarial proteins also needs to be addressed. Several recombinant antigens derived from blood-stage proteins have moved beyond basic research and are now poised for phase I trials in endemic countries. In this review we discuss the state of asexual blood-stage vaccines, focusing on recombinant antigens from Plasmodium falciparum. The significance of polymorphism and antigenic variation, the relevance of parasite immune evasion mechanisms, the need for reliable measures of successful intervention and new adjuvants are reviewed. Results from trials of asexual blood stage vaccine that support the continued effort to develop these antigens as key ingredients of multicomponent, multistage malaria vaccines are documented.
Key words: malaria, vaccine, blood stage, recombinant antigen, Plasmodium falciparum, clinical trials, antigenic polymorphism
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati 
Twitter What's this?
Related articles in JEB:
This article has been cited by other articles:
|
|
 |
|
  M. M. Lynch, A. Cernetich-Ott, W. P. Weidanz, and J. M. Burns Jr. Prediction of Merozoite Surface Protein 1 and Apical Membrane Antigen 1 Vaccine Efficacies against Plasmodium chabaudi Malaria Based on Prechallenge Antibody Responses Clin. Vaccine Immunol., March 1, 2009; 16(3): 293 - 302. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Miura, H. Zhou, S. E. Moretz, A. Diouf, M. A. Thera, A. Dolo, O. Doumbo, E. Malkin, D. Diemert, L. H. Miller, et al. Comparison of Biological Activity of Human Anti-Apical Membrane Antigen-1 Antibodies Induced by Natural Infection and Vaccination J. Immunol., December 15, 2008; 181(12): 8776 - 8783. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. M. Petritus and J. M. Burns Jr. Suppression of Lethal Plasmodium yoelii Malaria following Protective Immunization Requires Antibody-, IL-4-, and IFN-{gamma}-Dependent Responses Induced by Vaccination and/or Challenge Infection J. Immunol., January 1, 2008; 180(1): 444 - 453. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Dicko, I. Sagara, D. Diemert, M. Sogoba, M. B. Niambele, A. Dao, G. Dolo, D. Yalcouye, D. A. Diallo, A. Saul, et al. Year-to-Year Variation in the Age-Specific Incidence of Clinical Malaria in Two Potential Vaccine Testing Sites in Mali With Different Levels of Malaria Transmission Intensity Am J Trop Med Hyg, December 1, 2007; 77(6): 1028 - 1033. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Miura, H. Zhou, O. V. Muratova, A. C. Orcutt, B. Giersing, L. H. Miller, and C. A. Long In Immunization with Plasmodium falciparum Apical Membrane Antigen 1, the Specificity of Antibodies Depends on the Species Immunized Infect. Immun., December 1, 2007; 75(12): 5827 - 5836. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Ford, C. A. Lobo, M. Rodriguez, M. G. Zalis, R. L. D. Machado, A. R. B. Rossit, C. E. Cavasini, A. A. R. Couto, P. A. Enyong, and S. Lustigman Differential Antibody Responses to Plasmodium falciparum Invasion Ligand Proteins in Individuals Living in Malaria-Endemic Areas in Brazil and Cameroon Am J Trop Med Hyg, November 1, 2007; 77(5): 977 - 983. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X.-J. Cheng, H. Hayasaka, K. Watanabe, Y.-L. Tao, J.-Y. Liu, H. Tsukamoto, T. Horii, K. Tanabe, and H. Tachibana Production of High-Affinity Human Monoclonal Antibody Fab Fragments to the 19-Kilodalton C-Terminal Merozoite Surface Protein 1 of Plasmodium falciparum Infect. Immun., July 1, 2007; 75(7): 3614 - 3620. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. K. Parekh and T. L. Richie Characterization of Immune Reactivity Profiles Using Microarray Technology May Expedite Identification of Candidate Antigens for Next Generation Malaria Vaccines Clin. Chem., July 1, 2007; 53(7): 1183 - 1185. [Full Text] [PDF]
|
|
|
|
|
|
K. TANABE, N. SAKIHAMA, I. ROOTH, A. BJORKMAN, and A. FARNERT HIGH FREQUENCY OF RECOMBINATION-DRIVEN ALLELIC DIVERSITY AND TEMPORAL VARIATION OF PLASMODIUM FALCIPARUM MSP1 IN TANZANIA Am J Trop Med Hyg, June 1, 2007; 76(6): 1037 - 1045. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Shi, M. M. Lynch, M. Romero, and J. M. Burns Jr. Enhanced Protection against Malaria by a Chimeric Merozoite Surface Protein Vaccine Infect. Immun., March 1, 2007; 75(3): 1349 - 1358. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. P. A. Lusingu, A. T. R. Jensen, L. S. Vestergaard, D. T. Minja, M. B. Dalgaard, S. Gesase, B. P. Mmbando, A. Y. Kitua, M. M. Lemnge, D. Cavanagh, et al. Levels of Plasma Immunoglobulin G with Specificity against the Cysteine-Rich Interdomain Regions of a Semiconserved Plasmodium falciparum Erythrocyte Membrane Protein 1, VAR4, Predict Protection against Malarial Anemia and Febrile Episodes. Infect. Immun., May 1, 2006; 74(5): 2867 - 2875. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. R. PRATT-RICCIO, J. C. LIMA-JUNIOR, L. J. M. CARVALHO, M. THEISEN, E. C. ESPINDOLA-MENDES, F. SANTOS, J. OLIVEIRA-FERREIRA, A. C. GOLDBERG, C. T. DANIEL-RIBEIRO, and D. M. BANIC ANTIBODY RESPONSE PROFILES INDUCED BY PLASMODIUM FALCIPARUM GLUTAMATE-RICH PROTEIN IN NATURALLY EXPOSED INDIVIDUALS FROM A BRAZILIAN AREA ENDEMIC FOR MALARIA Am J Trop Med Hyg, December 1, 2005; 73(6): 1096 - 1103. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Scorza, K. Grubb, P. Smooker, A. Rainczuk, D. Proll, and T. W. Spithill Induction of Strain-Transcending Immunity against Plasmodium chabaudi adami Malaria with a Multiepitope DNA Vaccine Infect. Immun., May 1, 2005; 73(5): 2974 - 2985. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E.-T. HAN, T.-E. SONG, J.-H. PARK, E.-H. SHIN, S.-M. GUK, T.-Y. KIM, and J.-Y. CHAI ALLELIC DIMORPHISM IN THE MEROZOITE SURFACE PROTEIN-3{alpha} IN KOREAN ISOLATES OF PLASMODIUM VIVAX Am J Trop Med Hyg, December 1, 2004; 71(6): 745 - 749. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Rummel, J. Batchelder, P. Flaherty, G. LaFleur, P. Nanavati, J. M. Burns, and W. P. Weidanz CD28 Costimulation Is Required for the Expression of T-Cell-Dependent Cell-Mediated Immunity against Blood-Stage Plasmodium chabaudi Malaria Parasites Infect. Immun., October 1, 2004; 72(10): 5768 - 5774. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. L. Doolan, J. C. Aguiar, W. R. Weiss, A. Sette, P. L. Felgner, D. P. Regis, P. Quinones-Casas, J. R. Yates III, P. L. Blair, T. L. Richie, et al. Utilization of genomic sequence information to develop malaria vaccines J. Exp. Biol., November 1, 2003; 206(21): 3789 - 3802. [Abstract] [Full Text] [PDF]
|
|
