Abstract

Though Pfs25 has been shown to induce antibodies that can block parasite development in mosquitoes, the protein is poorly immunogenic. A water-in-oil adjuvant Montanide ISA 51 was able to enhance the immunogenicity of Pfs25;however, the formulation was too reactogenic and a Phase 1 human trial in the US to test the formulation had to be terminated before completion due to reactogenicity of the formulation. Thus the major challenge facing Pfs25-based TBV development is to find a formulation to increase immunogenicity and response longevity. ExoProtein A (EPA) has been used as a carrier for the Vi polysaccharide vaccine against typhoid fever. We have produced recombinant EPA (rEPA), and developed a process to conjugate Pfs25 with rEPA. Various conjugation chemistries and methods were evaluated for optimal immunogenicity and a robust conjugation processes. The biochemical properties of Pfs25-Pfs25 were characterized and the conjugates were evaluated in animals for their immunogenicity. The immune sera induced by the conjugate vaccine were tested for their ability to block parasite development in mosquitoes. A Phase 1 trial has been planned to test safety, immunogenicity, and ex-vivo transmission blocking activity in humans.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAAI001009-03
Application #
7964616
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
2009
Total Cost
$896,624
Indirect Cost

  Institution

Name
National Institute of Allergy and Infectious Diseases
Department
Type
DUNS #
City
State
Country
Zip Code

  Publications

Sagara, Issaka; Healy, Sara A; Assadou, Mahamadoun H et al. (2018) Safety and immunogenicity of Pfs25H-EPA/Alhydrogel, a transmission-blocking vaccine against Plasmodium falciparum: a randomised, double-blind, comparator-controlled, dose-escalation study in healthy Malian adults. Lancet Infect Dis 18:969-982
Scaria, Puthupparampil V; Chen, Beth; Rowe, Christopher G et al. (2017) Protein-protein conjugate nanoparticles for malaria antigen delivery and enhanced immunogenicity. PLoS One 12:e0190312
Coelho, Camila Henriques; Doritchamou, Justin Yai Alamou; Zaidi, Irfan et al. (2017) Advances in malaria vaccine development: report from the 2017 malaria vaccine symposium. NPJ Vaccines 2:34
Coulibaly, Mamadou B; Gabriel, Erin E; Sinaba, Youssouf et al. (2017) Optimizing Direct Membrane and Direct Skin Feeding Assays for Plasmodium falciparum Transmission-Blocking Vaccine Trials in Bancoumana, Mali. Am J Trop Med Hyg :
Assadou, Mahamadoun Hamady; Sagara, Issaka; Healy, Sara A et al. (2017) Malaria Infection and Gametocyte Carriage Rates in Preparation for Transmission Blocking Vaccine Trials in Bancoumana, Mali. Am J Trop Med Hyg 97:183-187
Brickley, Elizabeth B; Coulibaly, Mamadou; Gabriel, Erin E et al. (2016) Utilizing direct skin feeding assays for development of vaccines that interrupt malaria transmission: A systematic review of methods and case study. Vaccine 34:5863-5870
Jones, David S; Rowe, Christopher G; Chen, Beth et al. (2016) A Method for Producing Protein Nanoparticles with Applications in Vaccines. PLoS One 11:e0138761
MacDonald, Nicholas J; Nguyen, Vu; Shimp, Richard et al. (2016) Structural and Immunological Characterization of Recombinant 6-Cysteine Domains of the Plasmodium falciparum Sexual Stage Protein Pfs230. J Biol Chem 291:19913-22
Wu, Yimin; Sinden, Robert E; Churcher, Thomas S et al. (2015) Development of malaria transmission-blocking vaccines: from concept to product. Adv Parasitol 89:109-52
Hoffman, Stephen L; Vekemans, Johan; Richie, Thomas L et al. (2015) The march toward malaria vaccines. Vaccine 33 Suppl 4:D13-23

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