A Murine Model for Assessment of Plasmodium falciparum Transmission Blocking Vaccine using Transgenic Plasmodium berghei Parasites Expressing the target antigen Pfs25

Authors:
Mlambo G, Maciel J, Kumar N
In:
Source: Infect Immun
Publication Date: (2008)
Issue: 76(5): 2018-24
Research Area:
Parasitology
Cells used in publication:
Plasmodium berghei
Species: unicellular
Tissue Origin:
Platform:
Nucleofector® I/II/2b
Abstract
Currently, there is no animal model for Plasmodium falciparum challenge to evaluate malaria transmission blocking vaccines (TBV) based on well established Pfs25 target antigen. The biological activity of transmission blocking antibodies is 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 P. berghei to express Pfs25 and demonstrate 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 that of wild-type parasites and TrPfs25Pb displayed Pfs25 on the surface of ookinetes. Immune sera from non-human primates immunized with Pfs25 based vaccine when passively transferred to mice blocked transmission of TrPfs25Pb to An. stephensi. Furthermore, mice immunized with Pfs25 DNA vaccine and challenged with TrPfs25Pb displayed reduced malaria transmission as compared to mice immunized with wild-type plasmid. These studies describe development of an animal malaria model alternate to in vitro MFA and that it can facilitate P. falciparum transmission blocking vaccine evaluation based on the target antigen, Pfs25. We believe that using an animal model to test transmission blocking vaccines would be superior to MFA since there could be additional immune factors that may synergize transmission blocking activity of antibodies in vivo.