scholarly journals Plasmodium falciparum gametocyte transit through the cutaneous microvasculature: A new target for malaria transmission blocking vaccines?

2016 ◽  
Vol 12 (12) ◽  
pp. 3189-3195 ◽  
Author(s):  
Christian P. Nixon
Keyword(s):  
Plasmodium Falciparum ◽  
Malaria Transmission ◽  
Transmission Blocking ◽  
Transmission Blocking Vaccines

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

2005 ◽  
Vol 73 (11) ◽  
pp. 7375-7380 ◽  
Author(s):  
Takeshi Arakawa ◽  
Ai Komesu ◽  
Hitoshi Otsuki ◽  
Jetsumon Sattabongkot ◽  
Rachanee Udomsangpetch ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Malaria Transmission ◽  
Vaccine Candidate ◽  
Expression Patterns ◽  
Serum Antibody ◽  
Biologically Active ◽  
Mucosal Transmission ◽  
Transmission Blocking ◽  
Transmission Blocking Vaccines ◽  
Transmission Blocking Vaccine

ABSTRACT 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.

Malaria transmission-blocking vaccines: wheat germ cell-free technology can accelerate vaccine development

2019 ◽  
Vol 18 (10) ◽  
pp. 1017-1027
Author(s):  
Kazutoyo Miura ◽  
Mayumi Tachibana ◽  
Eizo Takashima ◽  
Masayuki Morita ◽  
Bernard N. Kanoi ◽  
...  
Keyword(s):  
Germ Cell ◽  
Malaria Transmission ◽  
Wheat Germ ◽  
Vaccine Development ◽  
Transmission Blocking ◽  
Transmission Blocking Vaccines

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

scholarly journals Malaria transmission-blocking conjugate vaccine in ALFQ adjuvant induces durable functional immune responses in rhesus macaques

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Puthupparampil V. Scaria ◽  
Charles Anderson ◽  
Olga Muratova ◽  
Nada Alani ◽  
Hung V. Trinh ◽  
...  
Keyword(s):  
Immune Responses ◽  
Malaria Transmission ◽  
Functional Activity ◽  
Rhesus Macaques ◽  
Transmission Blocking ◽  
Tlr4 Agonist ◽  
Functional Immunity ◽  
Antibody Levels ◽  
Transmission Blocking Vaccines ◽  
Better Than

AbstractMalaria transmission-blocking vaccines candidates based on Pfs25 and Pfs230 have advanced to clinical studies. Exoprotein A (EPA) conjugate of Pfs25 in Alhydrogel® developed functional immunity in humans, with limited durability. Pfs230 conjugated to EPA (Pfs230D1-EPA) with liposomal adjuvant AS01 is currently in clinical trials in Mali. Studies with these conjugates revealed that non-human primates are better than mice to recapitulate the human immunogenicity and functional activity. Here, we evaluated the effect of ALFQ, a liposomal adjuvant consisting of TLR4 agonist and QS21, on the immunogenicity of Pfs25-EPA and Pfs230D1-EPA in Rhesus macaques. Both conjugates generated strong antibody responses and functional activity after two vaccinations though activity declined rapidly. A third vaccination of Pfs230D1-EPA induced functional activity lasting at least 9 months. Antibody avidity increased with each vaccination and correlated strongly with functional activity. IgG subclass analysis showed induction of Th1 and Th2 subclass antibody levels that correlated with activity.

scholarly journals Saccharomyces cerevisiae-Secreted Fusion Proteins Pfs25 and Pfs28 Elicit Potent Plasmodium falciparum Transmission-Blocking Antibodies in Mice

1998 ◽  
Vol 66 (1) ◽  
pp. 59-64 ◽  
Author(s):  
Mary Margaret G. Gozar ◽  
Virginia L. Price ◽  
David C. Kaslow
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Plasmodium Falciparum ◽  
Fusion Proteins ◽  
Cell Epitope ◽  
Humoral Response ◽  
Chimeric Proteins ◽  
Transmission Blocking ◽  
Recombinant Fusion Proteins ◽  
Blocking Antibodies ◽  
Transmission Blocking Vaccines

ABSTRACT Transmission-blocking vaccines based on sexual-stage surface antigens of Plasmodium falciparum may assist in the control of this lethal form of human malaria. Two vaccine candidates, Pfs25 and Pfs28, were produced as single recombinant fusion proteins. The 39-kDa chimeric proteins, having a C-terminal His6 tag, were secreted by Saccharomyces cerevisiae, using the prepro-α-factor leader sequence. Pfs25-28 fusion proteins were significantly more potent than either Pfs25 or Pfs28 alone in eliciting antibodies in mice that blocked oocyst development in Anopheles freeborni mosquitoes: complete inhibition of oocyst development in the mosquito midgut was achieved with fewer vaccinations, at a lower dose, and for a longer duration than with either Pfs25 or Pfs28 alone. Increased antigen-specific immunoglobulin G titers and highly significant lymphoproliferative stimulation by Pfs28-containing antigens suggest the presence of an immunodominant helper T-cell epitope in the Pfs28 portion of the fusion proteins. This epitope may be responsible for the enhanced humoral response to both Pfs25 and Pfs28 antigens. Protein production of the fusion protein was improved 12-fold by converting Pfs28 codons to yeast-preferred codons (TBV28), using a modified ADH 2 promoter and incorporating a (Glu-Ala)2 repeat after the Kex2 cleavage site.

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