Abstract

The major challenge facing Pfs25-based TBV development is to find a formulation with great safety profile and capable of inducing sustained high antibody responses. The program has demonstrated that conjugating Pfs25 with carrier proteins OMPC of Neisseria meningitides, ExoProtein A (EPA) of Psuedomonas aeruginosa, or Pfs25 self, greatly enhance the immunogenicity of the recombinant Pfs25 produced in Pichia pastoris. Recombinant EPA (rEPA)has been produced, and a process developed to conjugate Pfs25 with rEPA. After evaluating various conjugation chemistries and methods, a robust conjugation process was developed, and manufacture of cGMP-grade Pfs25-EPA conjugate and formulated vaccine in a pilot manufacture facility occurred. The biochemical properties of Pfs25-EPA were characterized. Immunogenicity and safety of the conjugate formulated with various adjuvants were evaluated in animal studies. Pfs25-EPA/Alhydrogel was selected to be tested in humans. An Investigational New Drug Application was submitted to FDA for review, and a no-hold decision was made by FDA to allow proceed with the Phase 1 trial in US.

  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 #
1ZIAAI001009-05
Application #
8336231
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
2011
Total Cost
$2,085,065
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
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
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 :
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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