Accelerating Development of Transmission-Blocking Vaccines for Malaria Elimination Using a Novel Vaccine Candidate
This proposal aims at fast-tracking Pf75, which targets a different mode of action from the present transmission-blocking vaccine (TBV) candidates, such as Pfs25, once proof of principle is demonstrated and stage-gate requirements are met. The PATH Malaria Vaccine Initiative (MVI) will streamline development efforts in manufacture through identification of scalable expression systems; assess the functionality of the Pf75 novel TBV candidate through qualified SMFA, and suitability of process development and adjuvant formulation; and examine ways to evaluate combinations with existing target antigens, such as Pfs25, resulting in acting alone or synergistic enhancement of transmission-blocking activity. These activities will add value and benefits to the existing small and immature pipeline of TBVs.
Despite increased recent interest in the development of TBVs, only Plasmodium falciparum surface protein 25 (Pfs25) and the P. vivax homolog Pvs25 have been tested in Phase 1 clinical trials. Existing TBV candidates and formulations have not been optimized for expression, scalability, or the induction of high-titer functional antibodies in humans. As a result, the transmission-blocking pipeline is small and immature. The identification and rigorous testing of novel antigens is needed to expand the diversity of approaches under development.
The PATH Malaria Vaccine Initiative (MVI) has partnered with Ehime University to accelerate the development of a novel (Pf75) vaccine candidate. This project will need to meet predefined development stage-gates to determine whether Pf75 is a suitable candidate that meets the requirement for function (blocking parasite development in standard membrane feeding assays [SMFAs]), manufacture through identification of scalable expression systems, and suitability of process development and adjuvant formulation.