| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Department of Etiologic Biology, Second Military Medical University, Shanghai, China
A Plasmodium falciparum chimeric protein 2.9 (PfCP-2.9) was constructed consisting of the C-terminal regions of two leading malaria vaccine candidates, domain III of apical membrane ag-1 (AMA-1) and 19-kDa C-terminal fragment of the merozoite surface protein 1 (MSP1). The PfCP-2.9 was produced by Pichia pastoris in secreted form with a yield of 2600 mg/L and 
1 g/L of final product was obtained from a three-step purification process. Analysis of conformational properties of the chimeric protein showed that all six conformational mAbs interacted with the recombinant protein were reduction-sensitive, indicating that fusion of the two cysteine-rich proteins retains critical conformational epitopes. PfCP-2.9 was found to be highly immunogenic in rabbits as well as in rhesus monkeys (Macaca mulatta). The chimeric protein induced both anti-MSP1–19 and anti-AMA-1(III) Abs at levels 11- and 18-fold higher, respectively, than individual components did. Anti-PfCP-2.9 sera from both rabbits and rhesus monkeys almost completely inhibited in vitro growth of the P. falciparum FCC1/HN and 3D7 lines when tested at a 6.7-fold dilution. It was shown that the inhibition is dependent on the presence of Abs to the chimeric protein and their disulfide bond-dependent conformations. Moreover, the activity was mediated by a combination of growth-inhibitory Abs generated by the individual MSP1–19 and AMA-1(III) of PfCP-2.9. The combination of the extremely high yield of the protein and enhancement of its immune response provides a basis to develop an effective and affordable malaria vaccine.
This article has been cited by other articles:
|
|
 |
|
  J.-P. Carralot, C. Lemmel, S. Stevanovic, and S. Pascolo Mass spectrometric identification of an HLA-A*0201 epitope from Plasmodium falciparum MSP-1 Int. Immunol., November 1, 2008; 20(11): 1451 - 1456. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. J. Remarque, B. W. Faber, C. H. M. Kocken, and A. W. Thomas A Diversity-Covering Approach to Immunization with Plasmodium falciparum Apical Membrane Antigen 1 Induces Broader Allelic Recognition and Growth Inhibition Responses in Rabbits Infect. Immun., June 1, 2008; 76(6): 2660 - 2670. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Nebie, A. Diarra, A. Ouedraogo, I. Soulama, E. C. Bougouma, A. B. Tiono, A. T. Konate, R. Chilengi, M. Theisen, D. Dodoo, et al. Humoral Responses to Plasmodium falciparum Blood-Stage Antigens and Association with Incidence of Clinical Malaria in Children Living in an Area of Seasonal Malaria Transmission in Burkina Faso, West Africa Infect. Immun., February 1, 2008; 76(2): 759 - 766. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. W. Faber, E. J. Remarque, W. D. Morgan, C. H. M. Kocken, A. A. Holder, and A. W. Thomas Malaria Vaccine-Related Benefits of a Single Protein Comprising Plasmodium falciparum Apical Membrane Antigen 1 Domains I and II Fused to a Modified Form of the 19-Kilodalton C-Terminal Fragment of Merozoite Surface Protein 1 Infect. Immun., December 1, 2007; 75(12): 5947 - 5955. [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]
|
|
|
|
|
|
D. Zhang and W. Pan Evaluation of Three Pichia pastoris-Expressed Plasmodium falciparum Merozoite Proteins as a Combination Vaccine against Infection with Blood-Stage Parasites Infect. Immun., October 1, 2005; 73(10): 6530 - 6536. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
