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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

James M. Burns Jr.,1* Patrick R. Flaherty,2 Payal Nanavati,1 and William P. Weidanz1,2

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 JH–/– mice indicated that PcAMA-1 vaccine-induced immunity is largely antibody dependent. In contrast, JH–/– 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 {gamma}{delta} 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.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, Drexel University College of Medicine, 2900 Queen Ln., Philadelphia, PA 19129. Phone: (215) 991-8490. Fax: (215) 848-2271. E-mail: jburns{at}drexel.edu.

Editor: W. A. Petri, Jr.

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.



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