scholarly journals Anti-Pfs25 Human Plasma Reduces Transmission of Plasmodium falciparum Isolates That Have Diverse Genetic Backgrounds

2013 ◽  
Vol 81 (6) ◽  
pp. 1984-1989 ◽  
Author(s):  
Dari F. Da ◽  
Saurabh Dixit ◽  
Jetsumon Sattabonkot ◽  
Jianbing Mu ◽  
Luc Abate ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Burkina Faso ◽  
Phase 1 ◽  
Transmission Blocking ◽  
Content Type ◽  
Phase 1 Trial ◽  
Membrane Feeding ◽  
Geographical Regions ◽  
Reducing Activity ◽  
Membrane Feeding Assay

ABSTRACTPfs25 is a leading candidate for a malaria transmission-blocking vaccine whose potential has been demonstrated in a phase 1 trial with recombinant Pfs25 formulated with Montanide ISA51. Because of limited sequence polymorphism, the anti-Pfs25 antibodies induced by this vaccine are likely to have transmission-blocking or -reducing activity against most, if not all, field isolates. To test this hypothesis, we evaluated transmission-blocking activities by membrane feeding assay of anti-Pfs25 plasma from the Pfs25/ISA51 phase 1 trial againstPlasmodium falciparumparasites from patients in two different geographical regions of the world, Thailand and Burkina Faso. In parallel, parasite isolates from these patients were sequenced for the Pfs25 gene and genotyped for seven microsatellites. The results indicate that despite different genetic backgrounds among parasite isolates, the Pfs25 sequences are highly conserved, with a single nonsynonymous nucleotide polymorphism detected in 1 of 41 patients in Thailand and Burkina Faso. The anti-Pfs25 immune plasma had significantly higher transmission-reducing activity against parasite isolates from the two geographical regions than the nonimmune controls (P< 0.0001).

scholarly journals Functional Comparison of Plasmodium falciparum Transmission-Blocking Vaccine Candidates by the Standard Membrane-Feeding Assay

2013 ◽  
Vol 81 (12) ◽  
pp. 4377-4382 ◽  
Author(s):  
Kazutoyo Miura ◽  
Eizo Takashima ◽  
Bingbing Deng ◽  
Gregory Tullo ◽  
Ababacar Diouf ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Recombinant Proteins ◽  
The Other ◽  
Enzyme Linked Immunosorbent Assay ◽  
Dependent Manner ◽  
Feeding Assay ◽  
Transmission Blocking ◽  
Content Type ◽  
Membrane Feeding ◽  
Membrane Feeding Assay

ABSTRACTRecently, there has been a renewed interest in the development of transmission-blocking vaccines (TBV) againstPlasmodium falciparummalaria. While several candidate TBVs have been reported, studies directly comparing them in functional assays are limited. To this end, recombinant proteins of TBV candidates Pfs25, Pfs230, and PfHAP2 were expressed in the wheat germ cell-free expression system. Outbred CD-1 mice were immunized twice with the antigens. Two weeks after the second immunization, IgG levels were measured by enzyme-linked immunosorbent assay (ELISA), and IgG functionality was assessed by the standard membrane-feeding assay (SMFA) using culturedP. falciparumNF54 gametocytes andAnopheles stephensimosquitoes. All three recombinant proteins elicited similar levels of antigen-specific IgG judged by ELISA. When IgGs purified from pools of immune serum were tested at 0.75 mg/ml in the SMFA, all three IgGs showed 97 to 100% inhibition in oocyst intensity compared to control IgG. In two additional independent SMFA evaluations, anti-Pfs25, anti-Pfs230, and anti-PfHAP2 IgGs inhibited oocyst intensity in a dose-dependent manner. When all three data sets were analyzed, anti-Pfs25 antibody showed significantly higher inhibition than the other two antibodies (P< 0.001 for both), while there was no significant difference between the other two (P= 0.15). A proportion of plasma samples collected from adults living in an area of malaria endemicity in Mali recognized Pfs230 and PfHAP2. This is the first study showing that the HAP2 protein ofP. falciparumcan induce transmission-blocking antibody. The current study supports the possibility of using this system for a comparative study with multiple TBV candidates.

scholarly journals Evaluation of two Plasmodium vivax sexual stage antigens as transmission-blocking vaccine candidates

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Yongzhe Zhang ◽  
Fei Liu ◽  
Yan Zhao ◽  
Fan Yang ◽  
Jie Bai ◽  
...  
Keyword(s):  
Amino Acids ◽  
Plasmodium Vivax ◽  
Recombinant Proteins ◽  
Expression System ◽  
Anopheles Dirus ◽  
Transmission Blocking ◽  
Yeast Expression System ◽  
Membrane Feeding ◽  
Reducing Activity ◽  
Membrane Feeding Assay

Abstract Background Plasmodium vivax transmission-blocking vaccines (TBVs) are receiving increasing attention. Based on excellent transmission-blocking activities of the PbPH (PBANKA_0417200) and PbSOP26 (PBANKA_1457700) antigens in Plasmodium berghei, their orthologs in P. vivax, PVX_098655 (PvPH) and PVX_101120 (PvSOP26), were selected for the evaluation of their potential as TBVs. Methods Fragments of PvPH (amino acids 22–304) and PvSOP26 (amino acids 30–272) were expressed in the yeast expression system. The recombinant proteins were used to immunize mice to obtain antisera. The transmission-reducing activities of these antisera were evaluated using the direct membrane feeding assay (DMFA) using Anopheles dirus mosquitoes and P. vivax clinical isolates. Results The recombinant proteins PvPH and PvSOP26 induced robust antibody responses in mice. The DMFA showed that the anti-PvSOP26 sera significantly reduced oocyst densities by 92.0 and 84.1% in two parasite isolates, respectively, whereas the anti-PvPH sera did not show evident transmission-reducing activity. The variation in the DMFA results was unlikely due to the genetic polymorphisms of the two genes since their respective sequences were identical in the clinical P. vivax isolates. Conclusion PvSOP26 could be a promising TBV candidate for P. vivax, which warrants further evaluation. Graphical Abstract

Plasmodium falciparum Pf77 and male development gene 1 as vaccine antigens that induce potent transmission-reducing antibodies

2021 ◽  
Vol 13 (597) ◽  
pp. eabg2112
Author(s):  
Abhai K. Tripathi ◽  
Miranda S. Oakley ◽  
Nitin Verma ◽  
Godfree Mlambo ◽  
Hong Zheng ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Phase 1 ◽  
Biological Properties ◽  
Natural Immunity ◽  
Specific Expression ◽  
Transmission Blocking ◽  
Male Development ◽  
Malaria Vaccines ◽  
Membrane Feeding ◽  
Vaccine Antigens

Malaria vaccines that disrupt the Plasmodium life cycle in mosquitoes and reduce parasite transmission in endemic areas are termed transmission-blocking vaccines (TBVs). Despite decades of research, there are only a few Plasmodium falciparum antigens that indisputably and reproducibly demonstrate transmission-blocking immunity. So far, only two TBV candidates have advanced to phase 1/2 clinical testing with limited success. By applying an unbiased transcriptomics-based approach, we have identified Pf77 and male development gene 1 (PfMDV-1) as two P. falciparum TBV antigens that, upon immunization, induced antibodies that caused reductions in oocyst counts in Anopheles mosquito midguts in a standard membrane feeding assay. In-depth studies were performed to characterize the genetic diversity of, stage-specific expression by, and natural immunity to these two molecules to evaluate their suitability as TBV candidates. Pf77 and PfMDV-1 display limited antigenic polymorphism, are pan-developmentally expressed within the parasite, and induce naturally occurring antibodies in Ghanaian adults, which raises the prospect of natural boosting of vaccine-induced immune response in endemic regions. Together, these biological properties suggest that Pf77 and PfMDV-1 may warrant further investigation as TBV candidates.

scholarly journals The Spiroindolone Drug Candidate NITD609 Potently Inhibits Gametocytogenesis and Blocks Plasmodium falciparum Transmission to Anopheles Mosquito Vector

2012 ◽  
Vol 56 (7) ◽  
pp. 3544-3548 ◽  
Author(s):  
J. C. van Pelt-Koops ◽  
H. E. Pett ◽  
W. Graumans ◽  
M. van der Vegte-Bolmer ◽  
G. J. van Gemert ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Drug Candidate ◽  
Mosquito Vector ◽  
Content Type ◽  
Membrane Feeding ◽  
Dose Dependent Fashion ◽  
Dose Dependent ◽  
Membrane Feeding Assay ◽  
Reducing Potential

ABSTRACTThe global malaria agenda has undergone a reorientation from control of clinical cases to entirely eradicating malaria. For that purpose, a key objective is blocking transmission of malaria parasites from humans to mosquito vectors. The new antimalarial drug candidate NITD609 was evaluated for its transmission-reducing potential and compared to a few established antimalarials (lumefantrine, artemether, primaquine), using a suite ofin vitroassays. By the use of a microscopic readout, NITD609 was found to inhibit the early and late development ofPlasmodium falciparumgametocytesin vitroin a dose-dependent fashion over a range of 5 to 500 nM. In addition, using the standard membrane feeding assay, NITD609 was also found to be a very effective drug in reducing transmission to theAnopheles stephensimosquito vector. Collectively, our data suggest a strong transmission-reducing effect of NITD609 acting against differentP. falciparumtransmission stages.

Evaluation of two Plasmodium vivax sexual-stage antigens as transmission-blocking vaccine candidates

2021 ◽  
Author(s):  
Yongzhe Zhang ◽  
Fei Liu ◽  
Yan Zhao ◽  
Fan Yang ◽  
Jie Bai ◽  
...  
Keyword(s):  
Amino Acids ◽  
Plasmodium Vivax ◽  
Recombinant Proteins ◽  
Expression System ◽  
Transmission Blocking ◽  
Yeast Expression System ◽  
Membrane Feeding ◽  
Reducing Activity ◽  
Membrane Feeding Assay ◽  
Transmission Blocking Vaccines

Abstract Background: Plasmodium vivax transmission-blocking vaccines (TBVs) have received high attention. PVX_098655 (PvPH) and PVX_101120 (PvSOP26) were predicted to be potential TBV antigens based on the studies of their orthologs in Plasmodium berghei. Methods: Fragments of PvPH (amino acids 22–304) and PvSOP26 (amino acids 30–272) were expressed in the yeast expression system. The recombinant proteins were used to immunize mice to obtain the antisera. The transmission-reducing activities of these antisera were evaluated using the standard membrane feeding assay (SMFA) using Anopheles dirus mosquitoes and P. vivax clinical isolates. Results: The recombinant proteins PvPH and PvSOP26 induced robust antibody responses in mice. With SMFA, the anti-PvSOP26 sera significantly reduced oocyst densities by 92.0% and 84.1% in two parasite isolates, while the anti-PvPH sera did not show evident transmission-reducing activity. Both PvPH and PvSOP26 showed limited gene polymorphisms in the clinical P. vivax isolates. Conclusion: PvSOP26 could be a promising TBV candidate for P. vivax.

scholarly journals A Plant-Produced Pfs230 Vaccine Candidate Blocks Transmission of Plasmodium falciparum

2011 ◽  
Vol 18 (8) ◽  
pp. 1351-1357 ◽  
Author(s):  
Christine E. Farrance ◽  
Amy Rhee ◽  
R. Mark Jones ◽  
Konstantin Musiychuk ◽  
Moneim Shamloul ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Vaccine Candidate ◽  
Expression System ◽  
Leaf Tissue ◽  
Sexual Cycle ◽  
New Host ◽  
Transmission Blocking ◽  
Content Type ◽  
Block Transmission ◽  
Membrane Feeding

ABSTRACTPlasmodium falciparumis transmitted to a new host after completing its sexual cycle within a mosquito. Developing vaccines against the parasite sexual stages is a critical component in the fight against malaria. We are targeting multiple proteins ofP. falciparumwhich are found only on the surfaces of the sexual forms of the parasite and where antibodies against these proteins have been shown to block the progression of the parasite's life cycle in the mosquito and thus block transmission to the next human host. We have successfully produced a region of the Pfs230 antigen in our plant-based transient-expression system and evaluated this vaccine candidate in an animal model. This plant-produced protein, 230CMB, is expressed at approximately 800 mg/kg in fresh whole leaf tissue and is 100% soluble. Administration of 230CMB with >90% purity induces strong immune responses in rabbits with high titers of transmission-blocking antibodies, resulting in a greater than 99% reduction in oocyst counts in the presence of complement, as determined by a standard membrane feeding assay. Our data provide a clear perspective on the clinical development of a Pfs230-based transmission-blocking malaria vaccine.

scholarly journals Screening the Pathogen Box for Molecules Active against Plasmodium Sexual Stages Using a New Nanoluciferase-Based Transgenic Line of P. berghei Identifies Transmission-Blocking Compounds

2018 ◽  
Vol 62 (11) ◽  
Author(s):  
Juliana Calit ◽  
Irina Dobrescu ◽  
Xiomara A. Gaitán ◽  
Miriam H. Borges ◽  
Marisé S. Ramos ◽  
...  
Keyword(s):  
High Throughput Screening ◽  
Transmission Blocking ◽  
Content Type ◽  
Content Model ◽  
Mortality Burden ◽  
Membrane Feeding ◽  
Sexual Stages ◽  
Membrane Feeding Assay ◽  
Insight Into ◽  
Mosquito Infection

ABSTRACT Malaria remains an important parasitic disease with a large morbidity and mortality burden. Plasmodium transmission-blocking (TB) compounds are essential for achieving malaria elimination efforts. Recent efforts to develop high-throughput screening (HTS) methods to identify compounds that inhibit or kill gametocytes, the Plasmodium sexual stage infectious to mosquitoes, have yielded insight into new TB compounds. However, the activities of these compounds against gametes, formed in the first minutes of mosquito infection, are typically not assessed, unless screened in a standard membrane feeding assay, a labor-intensive assay. We demonstrate here the generation of a Plasmodium model for drug screens against gametes and fertilization. The new P. berghei line, named Ookluc, was genetically and pharmacologically validated and scalable for HTS. Screening the Pathogen Box from the Medicines for Malaria Venture using the new model identified promising TB compounds. The use of Ookluc in different libraries of compounds may aid in the identification of transmission-blocking drugs not assessed in screens against asexual stages or gametocytes.

scholarly journals Experimental Study: The Relationship between Plasmodium falciparum Gametocyte Carriage and Mosquitoes Infectiousness in Two Sympatric Ethnic Groups in Burkina Faso

2020 ◽  
pp. 1-9
Author(s):  
Samuel S. Serme ◽  
Noëlie H. Bere ◽  
Salif Sombie ◽  
Amidou Diarra ◽  
Desire Kargougou ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Burkina Faso ◽  
Ethnic Group ◽  
Ethnic Groups ◽  
Venous Blood ◽  
Plasmodium Falciparum Malaria ◽  
Feeding Assay ◽  
Membrane Feeding ◽  
Significant Difference ◽  
Membrane Feeding Assay

Aims: The lower susceptibility of the Fulani to malaria compared to Mossi was previously described in Burkina Faso in West Africa. The mature gametocyte stage of Plasmodium falciparum is known to be the only stage capable of infecting the mosquito though this process is disrupted by the action of immunity and other factors as well. Our study aims to assess the ability of two sympatric ethnic groups known to have different susceptibility to Plasmodium falciparum malaria, to infect mosquitoes through an experimental membrane feeding assay. Methodology: Study participants were gametocyte carriers aged from 2 to 12 years recruited in the village of Barkoundouba where Fulani and Mossi are living in sympatric. A venous blood was obtained from each participant for direct membrane feeding assay of insectary reared mosquitoes. Blood fed mosquitoes were stored for 7 days with sugar water as the only food source, then dissected for the microscopic detection for oocysts. Results: A total of 1050 mosquitoes were used for the experimental infections. Eight day after feeding, a total of 897 mosquitoes were dissected, 275 from the Fulani and 622 from the Mossi group. With an average of 43 stomachs examined by experimentation, the mosquito infestation rate was 10.5% in Fulani and 13.2% in Mossi group (p=0.569). The fed mosquito rate was 95 % and 95.6% in Fulani and Mossi ethnic group respectively (p=0.241). The rate of survival mosquitoes after the feeding was 96.5% and 87.5% in Fulani and Mossi ethnic group respectively (p=0.088). The proportion of dissected mosquitoes was 100% and 99.2% in Fulani and Mossi ethnic group respectively (p=0.138) leading to an average oocystic load of 249 in Fulani and 21 in Mossi group. The success rate of DMFA in both groups combined was 57.14%. Indeed, this rate was 33.33% and 66.67% in Fulani and Mossi group respectively. Conclusion: Our study showed that there is no significant difference found between the two ethnic group with the fed, survival, dissected and the infested mosquitoes rate. However, the average of oocystic load was higher in Fulani than the Mossi group despite the low infection in Fulani group. There is a need to explore the mechanism underlying such difference between the two ethnic groups.

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