This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Burns, J. M. Articles by Weidanz, W. P. Search for Related Content PubMed PubMed Citation Articles by Burns, J. M., Jr. Articles by Weidanz, W. P.

 Previous Article  |  Next Article 

Infection and Immunity, October 2004, p. 5605-5612, Vol. 72, No. 10
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.10.5605-5612.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Protection against Plasmodium chabaudi Malaria Induced by Immunization with Apical Membrane Antigen 1 and Merozoite Surface Protein 1 in the Absence of Gamma Interferon or Interleukin-4

Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania,¹ Department of Medical Microbiology and Immunology, University of Wisconsin, Madison, Wisconsin²

Received 22 April 2004/ Returned for modification 1 June 2004/ Accepted 24 June 2004

Strategies to optimize formulations of multisubunit malaria vaccines require a basic knowledge of underlying protective immune mechanisms induced by each vaccine component. In the present study, we evaluated the contribution of antibody-mediated and cell-mediated immune mechanisms to the protection induced by immunization with two blood-stage malaria vaccine candidate antigens, apical membrane antigen 1 (AMA-1) and merozoite surface protein 1 (MSP-1). Immunologically intact or selected immunologic knockout mice were immunized with purified recombinant Plasmodium chabaudi AMA-1 (PcAMA-1) and/or the 42-kDa C-terminal processing fragment of P. chabaudi MSP-1 (MSP-1₄₂). The efficacy of immunization in each animal model was measured as protection against blood-stage P. chabaudi malaria. Immunization of B-cell-deficient J_H^–/– mice indicated that PcAMA-1 vaccine-induced immunity is largely antibody dependent. In contrast, J_H^–/– mice immunized with PcMSP-1₄₂ were partially protected against P. chabaudi malaria, indicating a role for protective antibody-dependent and antibody-independent mechanisms of immunity. The involvement of T cells in vaccine-induced PcAMA-1 and/or PcMSP-1₄₂ protection was minor. Analysis of the isotypic profile of antigen-specific antibodies induced by immunization of immunologically intact mice revealed a dominant IgG1 response. However, neither interleukin-4 and the production of IgG1 antibodies nor gamma interferon and the production of IgG2a/c antibodies were essential for PcAMA-1 and/or PcMSP-1₄₂ vaccine-induced protection. Therefore, for protective antibody-mediated immunity, vaccine adjuvants and delivery systems for AMA-1- and MSP-1-based vaccines can be selected for their ability to maximize responses irrespective of IgG isotype or any Th1 versus Th2 bias in the CD4⁺-T-cell response.

Editor: W. A. Petri, Jr.

This article has been cited by other articles:

• Remarque, E. J., Faber, B. W., Kocken, C. H. M., Thomas, A. W. (2008). 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. 76: 2660-2670 [Abstract] [Full Text]  
• Petritus, P. M., Burns, J. M. Jr. (2008). 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. 180: 444-453 [Abstract] [Full Text]  
• Miura, K., Zhou, H., Muratova, O. V., Orcutt, A. C., Giersing, B., Miller, L. H., Long, C. A. (2007). In Immunization with Plasmodium falciparum Apical Membrane Antigen 1, the Specificity of Antibodies Depends on the Species Immunized. Infect. Immun. 75: 5827-5836 [Abstract] [Full Text]  
• Shi, Q., Lynch, M. M., Romero, M., Burns, J. M. Jr. (2007). Enhanced Protection against Malaria by a Chimeric Merozoite Surface Protein Vaccine. Infect. Immun. 75: 1349-1358 [Abstract] [Full Text]  
• van der Heyde, H. C., Batchelder, J. M., Sandor, M., Weidanz, W. P. (2006). Splenic {gamma}{delta} T Cells Regulated by CD4+ T Cells Are Required To Control Chronic Plasmodium chabaudi Malaria in the B-Cell-Deficient Mouse.. Infect. Immun. 74: 2717-2725 [Abstract] [Full Text]