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Infection and Immunity, November 2005, p. 7375-7380, Vol. 73, No. 11
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.11.7375-7380.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Nasal Immunization with a Malaria Transmission-Blocking Vaccine Candidate, Pfs25, Induces Complete Protective Immunity in Mice against Field Isolates of Plasmodium falciparum

Division of Molecular Microbiology, Center of Molecular Biosciences, University of the Ryukyus, Nishihara, Okinawa 903-0213, Japan,¹ Department of Molecular Parasitology, Ehime University School of Medicine, Toon, Ehime 791-0295, Japan,² Department of Entomology, Armed Forces Research Institute of Medical Sciences, Bangkok 10400, Thailand,³ Department of Pathobiology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand,⁴ Laboratory of Global Animal Resource Science, Graduate School of Agricultural and Life Sciences, University of Tokyo, Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan,⁵ Laboratory of Parasitic Diseases, National Institute of Animal Health, National Agricultural Research Organization, Tsukuba, Ibaraki 305-0856, Japan,⁶ Malaria Vaccine Development Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland 20852,⁷ Cell-Free Science and Technology Research Center, Ehime University, Matsuyama, Ehime 790-8577, Japan⁸

Received 28 June 2005/ Returned for modification 25 July 2005/ Accepted 20 August 2005

Malaria transmission-blocking vaccines based on antigens expressed in sexual stages of the parasites are considered one promising strategy for malaria control. To investigate the feasibility of developing noninvasive mucosal transmission-blocking vaccines against Plasmodium falciparum, intranasal immunization experiments with Pichia pastoris-expressed recombinant Pfs25 proteins were conducted. Mice intranasally immunized with the Pfs25 proteins in the presence of a potent mucosal adjuvant cholera toxin induced robust systemic as well as mucosal antibodies. All mouse immunoglobulin G (IgG) subclasses except IgG3 were found in serum at comparable levels, suggesting that the immunization induced mixed Th1 and Th2 responses. Consistent with the expression patterns of the Pfs25 proteins in the parasites, the induced immune sera specifically recognized ookinetes but not gametocytes. In addition, the immune sera recognized Pfs25 proteins with the native conformation but not the denatured forms, indicating that mucosal immunization induced biologically active antibodies capable of recognizing conformational epitopes of native Pfs25 proteins. Feeding Anopheles dirus mosquitoes with a mixture of the mouse immune sera and gametocytemic blood derived from patients infected with P. falciparum resulted in complete interference with oocyst development in mosquito midguts. The observed transmission-blocking activities were strongly correlated with specific serum antibody titers. Our results demonstrated for the first time that a P. falciparum transmission-blocking vaccine candidate is effective against field-isolated parasites and may justify the investigation of noninvasive mucosal vaccination regimens for control of malaria, a prototypical mucosa-unrelated mosquito-borne parasitic disease.

Editor: W. A. Petri, Jr.

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