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. The trial is in progress and the vaccine was demonstrated to be safe.

  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 #
1ZIAAI001009-06
Application #
8555932
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
2012
Total Cost
$4,033,409
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
Hoffman, Stephen L; Vekemans, Johan; Richie, Thomas L et al. (2015) The March Toward Malaria Vaccines. Am J Prev Med 49:S319-33
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

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