scholarly journals Comparison and Optimization of Different Methods for theIn VitroProduction ofPlasmodium falciparumGametocytes

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
María Roncalés ◽  
Jaume Vidal-Mas ◽  
Didier Leroy ◽  
Esperanza Herreros
Keyword(s):  
Plasmodium Falciparum ◽  
Malaria Transmission ◽  
Improved Method ◽  
Transmission Blocking ◽  
Blocking Malaria Transmission

The generation of sexually committed parasites (gametocytogenesis) is poorly understood in malaria. If the mechanisms regulating this process were elucidated, new opportunities for blocking malaria transmission could be revealed. Here we compare several methods described previously for thein vitroproduction ofPlasmodium falciparumgametocytes. Our approach relies on the combination of several factors that we demonstrated as impacting on or being critical to gametocytogenesis. An improved method has been developed for thein vitroproduction ofP. falciparumgametocytes as the first step toward obtaining adequate numbers of pure gametocytes forin vitrostudies, such as, for example, the identification of transmission blocking drugs.

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

2008 ◽  
Vol 76 (5) ◽  
pp. 2018-2024 ◽  
Author(s):  
Godfree Mlambo ◽  
Jorge Maciel ◽  
Nirbhay Kumar
Keyword(s):  
Animal Model ◽  
Plasmodium Falciparum ◽  
Malaria Transmission ◽  
Plasmodium Berghei ◽  
Target Antigen ◽  
Wild Type ◽  
Transmission Blocking ◽  
Transmission Blocking Vaccines ◽  
Transmission Blocking Vaccine

ABSTRACT 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.

scholarly journals An improved method for the in vitro differentiation of Plasmodium falciparum gametocytes into ookinetes

2010 ◽  
Vol 9 (1) ◽  
pp. 194 ◽  
Author(s):  
Anil K Ghosh ◽  
Rhoel R Dinglasan ◽  
Hiromi Ikadai ◽  
Marcelo Jacobs-Lorena
Keyword(s):  
Plasmodium Falciparum ◽  
In Vitro Differentiation ◽  
Improved Method

scholarly journals Engineering a Virus-Like Particle as an Antigenic Platform for a Pfs47-Targeted Malaria Transmission-Blocking Vaccine

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Lampouguin Yenkoidiok-Douti ◽  
Adeline E. Williams ◽  
Gaspar E. Canepa ◽  
Alvaro Molina-Cruz ◽  
Carolina Barillas-Mury
Keyword(s):  
Plasmodium Falciparum ◽  
Amino Acid ◽  
Malaria Transmission ◽  
Transmission Blocking ◽  
High Affinity ◽  
Virus Like Particle ◽  
Antibody Titers ◽  
Reducing Activity ◽  
Sexual Stages ◽  
Transmission Blocking Vaccine

AbstractWe recently characterized Pfs47, a protein expressed on the surface of sexual stages and ookinetes of Plasmodium falciparum, as a malaria transmission-blocking vaccine (TBV) target. Mice immunization induced antibodies that conferred strong transmission-reducing activity (TRA) at a concentration of 200 μg/mL. Here, we sought to optimize the Pfs47 vaccine to elicit higher titers of high-affinity antibodies, capable of inducing strong TRA at a lower concentration. We report the development and evaluation of a Pfs47-based virus-like particle (VLP) vaccine generated by conjugating our 58 amino acid Pfs47 antigen to Acinetobacter phage AP205-VLP using the SpyCatcher:SpyTag adaptor system. AP205-Pfs47 complexes (VLP-P47) formed particles of ~22 nm diameter that reacted with polyclonal anti-Pfs47 antibodies, indicating that the antigen was accessible on the surface of the particle. Mice immunized with VLP-P47 followed by a boost with Pfs47 monomer induced significantly higher antibody titers, with higher binding affinity to Pfs47, than mice that received two immunizations with either VLP-P47 (VLP-P47/VLP-P47) or the Pfs47 monomer (P47/P47). Purified IgG from VLP-P47/P47 mice had strong TRA (83–98%) at concentrations as low as 5 μg/mL. These results indicate that conjugating the Pfs47 antigen to AP205-VLP significantly enhanced antigenicity and confirm the potential of Pfs47 as a TBV candidate.

scholarly journals A simple and predictive phenotypic High Content Imaging assay for Plasmodium falciparum mature gametocytes to identify malaria transmission blocking compounds

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Leonardo Lucantoni ◽  
Francesco Silvestrini ◽  
Michele Signore ◽  
Giulia Siciliano ◽  
Maarten Eldering ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Malaria Transmission ◽  
Transmission Blocking ◽  
High Content Imaging

scholarly journals Assessment in vitro of the antimalarial and transmission blocking activities of Cipargamin and Ganaplacide in artemisinin resistant Plasmodium falciparum

2022 ◽  
Author(s):  
Achaporn Yipsirimetee ◽  
Pornpawee Chiewpoo ◽  
Rupam Tripura ◽  
Dysoley Lek ◽  
Nicholas P. J. Day ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Antimalarial Activity ◽  
Artemisinin Resistance ◽  
Blood Stage ◽  
Mature Stage ◽  
Asexual Blood Stage ◽  
Male And Female ◽  
Transmission Blocking ◽  
Combination Treatments

Artemisinin resistance in Plasmodium falciparum has emerged and spread widely in the Greater Mekong Subregion threatening current first line artemisinin combination treatments. New antimalarial drugs are needed urgently. Cipargamin (KAE609) and ganaplacide (KAF156) are promising novel antimalarial compounds in advanced stages of development. Both compounds have potent asexual blood stage activities, inhibit P. falciparum gametocytogenesis and reduce oocyst development in anopheline mosquitoes. In this study, we compared the asexual and sexual stage activities of cipargamin, ganaplacide and artesunate in artemisinin resistant P. falciparum isolates (N=7, K13 mutation; C580Y, G449A and R539T) from Thailand and Cambodia. Asexual blood stage antimalarial activity was evaluated in a SYBR-green I based 72h in vitro assay, and the effects on male and female mature stage V gametocytes were assessed in the P. falciparum dual gamete formation assay. Ganaplacide had higher activities when compared to cipargamin and artesunate, with a mean (SD) IC50 against asexual stages of 5.5 (1.1) nM, 7.8 (3.9) nM for male gametocytes and 57.9 (59.6) nM for female gametocytes. Cipargamin had a similar potency against male and female gametocytes, with a mean (SD) IC50 of 123.1 (80.2) nM for male gametocytes, 88.5 (52.7) nM for female gametocytes and 2.4 (0.6) nM for asexual stages. Both cipargamin and ganaplacide showed significant transmission-blocking activities against artemisinin resistant P. falciparum in vitro .

Plasmodium falciparum: Immunogenicity of Alum-Adsorbed Clinical-Grade TBV25–28, a Yeast-Secreted Malaria Transmission-Blocking Vaccine Candidate

2001 ◽  
Vol 97 (2) ◽  
pp. 61-69 ◽  
Author(s):  
Mary Margaret G Gozar ◽  
Olga Muratova ◽  
David B Keister ◽  
Charlotte R Kensil ◽  
Virginia L Price ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Malaria Transmission ◽  
Vaccine Candidate ◽  
Clinical Grade ◽  
Transmission Blocking ◽  
Transmission Blocking Vaccine
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