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.

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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
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