scholarly journals 5-Aminopyrazole-4-carboxamide analogues are selective inhibitors of Plasmodium falciparum microgametocyte exflagellation and potential malaria transmission blocking agents

2016 ◽  
Vol 26 (22) ◽  
pp. 5487-5491 ◽  
Author(s):  
Wenlin Huang ◽  
Matthew A. Hulverson ◽  
Zhongsheng Zhang ◽  
Ryan Choi ◽  
Kevin J. Hart ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Malaria Transmission ◽  
Selective Inhibitors ◽  
Transmission Blocking ◽  
Blocking Agents

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 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 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

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

scholarly journals Display of malaria transmission-blocking antigens on chimeric duck hepatitis B virus-derived virus-like particles produced inHansenula polymorpha

2019 ◽  
Author(s):  
David Wetzel ◽  
Jo-Anne Chan ◽  
Manfred Suckow ◽  
Andreas Barbian ◽  
Michael Weniger ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Malaria Transmission ◽  
Transmission Blocking ◽  
Duck Hepatitis B Virus ◽  
Vaccine Candidates ◽  
Duck Hepatitis ◽  
B Virus ◽  
Transmission Blocking Vaccine

1.AbstractBackgroundMalaria caused byPlasmodium falciparumis one of the major threats to human health globally. Despite huge efforts in malaria control and eradication, highly effective vaccines are urgently needed, including vaccines that can block malaria transmission. Chimeric virus-like particles (VLP) have emerged as a promising strategy to develop new malaria vaccine candidates.MethodsWe developed yeast cell lines and processes for the expression of malaria transmission-blocking vaccine candidates Pfs25 and Pfs230 as VLP and VLP were analyzed for purity, size, protein incorporation rate and expression of malaria antigens.ResultsIn this study, a novel platform for the display ofPlasmodium falciparumantigens on chimeric VLP is presented. Leading transmission-blocking vaccine candidates Pfs25 and Pfs230 were genetically fused to the small surface protein (dS) of the duck hepatitis B virus (DHBV). The resulting fusion proteins were co-expressed in recombinantHansenula polymorpha(syn.Pichia angusta, Ogataea polymorpha) strains along with the wild-type dS as the VLP scaffold protein. Through this strategy, chimeric VLP containing Pfs25 or the Pfs230-derived fragments Pfs230c or Pfs230D1M were purified. Up to 100 mg chimeric VLP were isolated from 100 g dry cell weight with a maximum protein purity of 90 % on the protein level. Expression of the Pfs230D1M construct was more efficient than Pfs230c and enabled VLP with higher purity. VLP showed reactivity with transmission-blocking antibodies and supported the surface display of the malaria antigens on the native VLP.ConclusionThe incorporation of leadingPlasmodium falciparumtransmission-blocking antigens into the dS-based VLP scaffold is a promising novel strategy for their display on nano-scaled particles. Competitive processes for efficient production and purification were established in this study.

scholarly journals Restricted or absent immune responses in human populations to Plasmodium falciparum gamete antigens that are targets of malaria transmission-blocking antibodies.

1989 ◽  
Vol 169 (1) ◽  
pp. 135-147 ◽  
Author(s):  
R Carter ◽  
P M Graves ◽  
I A Quakyi ◽  
M F Good
Keyword(s):  
Immune Response ◽  
Plasmodium Falciparum ◽  
Antibody Response ◽  
Malaria Transmission ◽  
Surface Antigens ◽  
Surface Proteins ◽  
Human Populations ◽  
Sexual Stage ◽  
Transmission Blocking ◽  
Blocking Antibodies

We have studied the antibodies to sexual stage antigens of Plasmodium falciparum in human sera from Papua New Guinea where intense transmission of P. falciparum occurs as well as the less prevalent P. malariae and P. vivax. In extracts of gametes of P. falciparum we have studied the reactivity of serum antibodies with antigens labeled with 125I on the surface of the gametes as well as intracellular gamete antigens. A prominent 27-kD sexual stage-specific intracellular protein was recognized more or less in proportion to the general antibody response to gamete proteins. The response to the gamete surface proteins, however, was quite unrepresentative of the general antibody response to the intracellular gamete proteins. No antibodies were detected against Pfs25, a 21-kD protein expressed on zygotes and ookinetes of P. falciparum and known to be a sensitive target of malaria transmission-blocking antibodies. The antibody response to two other target antigens of transmission-blocking antibodies on the surface of gametes of P. falciparum, a 230- and a 48- and 45-kD protein doublet, was very variable and independent of the response to the internal protein antigens. Several possibilities are discussed that may account for the variable response to these gamete surface antigens in individuals with otherwise good antibody responses to internal sexual stage proteins. Among these is the possibility that there is MHC restriction of the immune response to the gamete surface antigens in the human population. This interpretation accords well with evidence for MHC-restricted immune response to the same P. falciparum gamete surface antigens in studies with H-2 congenic mice (24).

scholarly journals Correctly folded Pfs48/45 protein of Plasmodium falciparum elicits malaria transmission-blocking immunity in mice

2008 ◽  
Vol 105 (11) ◽  
pp. 4301-4305 ◽  
Author(s):  
N. S. Outchkourov ◽  
W. Roeffen ◽  
A. Kaan ◽  
J. Jansen ◽  
A. Luty ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Malaria Transmission ◽  
Transmission Blocking
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