PRODUCT DEVELOPMENT OF A MEMBRANE TETRASPANIN VACCINE AGAINST SCHISTOSOMIASIS - Schistosomiasis is one of the most important neglected tropical diseases affecting over 200 million people in
low-income countries, and causing a global disease burden that may exceed malaria. The current approach to
schistosomiasis control relies on mass drug administration with praziquantel, but high rates of post-treatment
re-infection, rebound morbidity, and concerns about drug resistance have led to urgent calls for antischistisosome
vaccine development. A new class of schistosome antigens showing great promise as vaccine
candidates has been recently discovered through high throughput proteomics of the parasite¿s outer syncytial
surface (tegument) together with targeted host immunity from putatively resistant individuals. From this
analysis a tetrapanin surface antigen from Schistosoma mansoni and known as Sm-TSP-2 has emerged. In
multiple animals trials this antigen elicits high levels of protective immunity when formulated with alum and is
selectively recognized by a subset of individuals resistant to S. mansoni infection in Brazil. The Sabin Vaccine
Institute is a product development public private partnership with a track record of transitioning safe and effect
recombinant vaccines for neglected tropical diseases from discovery to the clinic. Through this proposal Sabin
will embark on a milestone-driven mid-stage product development project for the Sm-TSP-2 vaccine to combat
intestinal schistosomiasis; cGMP manufacture and regulatory submission in the United States and Brazil will
represent the major deliverables at the end of the funding period. To achieve these milestones, Sabin will first
develop a reproducible manufacturing process at the 10 liter scale for the fermentation and purification of a
yeast-derived recombinant antigen. The feasibility of the process is based on substantial preliminary data.
Once process development is completed the process and formulation technology will be transferred to Instituto
Butantan, a highly accomplished public-sector manufacturer in Brazil, in order to produce vaccine at the 60 liter
scale. Lot release and stability testing will be performed on the manufactured vaccine. Among the innovations
in this proposal, the recombinant antigen will undergo biophysical profiling (i.e., circular dichroism,
fluorescence, and light scattering), together with GRAS (generally regarded as safe)-designated exicpietns and
stabilizers, in order to maximize the stability of the bulk antigens. In addition, a potency test with novel
statistical methodologies will be developed. To ensure success in achieving milestones, Sabin will partner with
a commercial risk management team and work closely with external advisors collectively having over 100
years of vaccine development and manufacturing experience.
