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. Previously the LMIV has demonstrated that conjugating Pfs25 with carrier protein ExoProtein A (EPA) of Psuedomonas aeruginosa greatly enhance the immunogenicity of the recombinant Pfs25 produced in Pichia pastoris. A process was developed to conjugate Pfs25 with rEPA, and cGMP-grade Pfs25-EPA conjugate was manufactured and formulated with Alhydrogel. A Phase 1 trial was conducted in US. After demonstrating that vaccine was safe, immunogenic, and could induce transmission reducing activity in US vaccinees, LMIV has now completed a Phase 1 trial in Mali, the first time in the world evaluating the safety, immunogenicity, and transmission blocking activity of a vaccine in a target population. The results of these studies have demonstrated that transmission blocking activity can be induced in both US and Malian vaccinees. However, the antibodies induced by this vaccine when formulated with Alhydrogel are short-lived, and hence improvements to the vaccine are required to achieve the activity thought to be needed for malaria elimination campaigns.

  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 #
1ZIAAI001009-09
Application #
9161592
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
9
Fiscal Year
2015
Total Cost
Indirect Cost

  Institution

Name
Niaid Extramural Activities
Department
Type
DUNS #
City
State
Country
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  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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