Malaria Vaccine: Pfs25-rEPA

Duffy, Patrick

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. We have 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. 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-EPA were characterized and the conjugates were evaluated in animals for their immunogenicities. The immune sera induced by the conjugate vaccine blocked parasite development in mosquitoes. A process was developed to produce a pilot scale cGMP lot conjugate. Animal studies were conducted to evaluate enhancement of immunogenicity by novel adjuvants. 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 #: 1ZIAAI001009-04
• Application #: 8157008
• Support Year: 4
• Fiscal Year: 2010
• Total Cost: $2,036,508

Institution

• Name: National Institute of Allergy and Infectious Diseases

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