scholarly journals Characterization of a Plasmodium berghei sexual stage antigen PbPH as a new candidate for malaria transmission-blocking vaccine

2016 ◽  
Vol 9 (1) ◽  
Author(s):  
Xu Kou ◽  
Wenqi Zheng ◽  
Feng Du ◽  
Fei Liu ◽  
Meilian Wang ◽  
...  
Keyword(s):  
Malaria Transmission ◽  
Plasmodium Berghei ◽  
Sexual Stage ◽  
Transmission Blocking ◽  
Transmission Blocking Vaccine

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 Potent antibody lineage against malaria transmission elicited by human vaccination with Pfs25

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Brandon McLeod ◽  
Kazutoyo Miura ◽  
Stephen W. Scally ◽  
Alexandre Bosch ◽  
Ngan Nguyen ◽  
...  
Keyword(s):  
Malaria Transmission ◽  
Affinity Maturation ◽  
Human Antibody ◽  
Blocking Antibody ◽  
Transmission Blocking ◽  
Clinical Models ◽  
Humoral Responses ◽  
Transmission Blocking Vaccines ◽  
Transmission Blocking Vaccine

Abstract Transmission-blocking vaccines have the potential to be key contributors to malaria elimination. Such vaccines elicit antibodies that inhibit parasites during their development in Anopheles mosquitoes, thus breaking the cycle of transmission. To date, characterization of humoral responses to Plasmodium falciparum transmission-blocking vaccine candidate Pfs25 has largely been conducted in pre-clinical models. Here, we present molecular analyses of human antibody responses generated in a clinical trial evaluating Pfs25 vaccination. From a collection of monoclonal antibodies with transmission-blocking activity, we identify the most potent transmission-blocking antibody yet described against Pfs25; 2544. The interactions of 2544 and three other antibodies with Pfs25 are analyzed by crystallography to understand structural requirements for elicitation of human transmission-blocking responses. Our analyses provide insights into Pfs25 immunogenicity and epitope potency, and detail an affinity maturation pathway for a potent transmission-blocking antibody in humans. Our findings can be employed to guide the design of improved malaria transmission-blocking vaccines.

scholarly journals Evaluation of two lead malaria transmission blocking vaccine candidate antibodies in natural parasite-vector combinations

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Anais Bompard ◽  
Dari F. Da ◽  
Rakiswendé S. Yerbanga ◽  
Sumi Biswas ◽  
Melissa Kapulu ◽  
...  
Keyword(s):  
Malaria Transmission ◽  
Vaccine Candidate ◽  
Transmission Blocking ◽  
Transmission Blocking Vaccine

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.

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