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Infection and Immunity, May 2008, p. 2018-2024, Vol. 76, No. 5
0019-9567/08/$08.00+0     doi:10.1128/IAI.01409-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Murine Model for Assessment of Plasmodium falciparum Transmission-Blocking Vaccine Using Transgenic Plasmodium berghei Parasites Expressing the Target Antigen Pfs25

Malaria Research Institute, Johns Hopkins Bloomberg School of Public Health, Department of Molecular Microbiology and Immunology, 615 N. Wolfe Street, Baltimore, Maryland 21205

Received 18 October 2007/ Returned for modification 27 November 2007/ Accepted 19 February 2008

Currently, there is no animal model for Plasmodium falciparum challenge to evaluate malaria transmission-blocking vaccines based on the well-established Pfs25 target antigen. The biological activity of transmission-blocking antibodies is typically assessed using an assay known as the membrane feeding assay (MFA). It is an in vitro method that involves mixing antibodies with cultured P. falciparum gametocytes and feeding them to mosquitoes through an artificial membrane followed by assessment of infection in the mosquitoes. We genetically modified Plasmodium berghei to express Pfs25 and demonstrated that the transgenic parasites (TrPfs25Pb) are susceptible to anti-Pfs25 antibodies during mosquito-stage development. The asexual growth kinetics and mosquito infectivity of TrPfs25Pb were comparable to those of wild-type parasites, and TrPfs25Pb displayed Pfs25 on the surface of ookinetes. Immune sera from nonhuman primates immunized with a Pfs25-based vaccine when passively transferred to mice blocked transmission of TrPfs25Pb to Anopheles stephensi. Furthermore, mice immunized with Pfs25 DNA vaccine and challenged with TrPfs25Pb displayed reduced malaria transmission compared to mice immunized with wild-type plasmid. These studies describe development of an animal malaria model alternative to the in vitro MFA and show that the model can facilitate P. falciparum transmission-blocking vaccine evaluation based on the target antigen Pfs25. We believe that an animal model to test transmission-blocking vaccines would be superior to the MFA, since there may be additional immune factors that synergize the transmission-blocking activity of antibodies in vivo.

Published ahead of print on 3 March 2008.

Editor: J. F. Urban, Jr.

This article has been cited by other articles:

• Mlambo, G., Kumar, N. (2008). Transgenic Rodent Plasmodium berghei Parasites as Tools for Assessment of Functional Immunogenicity and Optimization of Human Malaria Vaccines. Eukaryot Cell 7: 1875-1879 [Full Text]