The major challenges facing Pvs230D1-based TBV development are the following: 1) cGMP manufacturing of a Pvs230D1-EPA conjugated nanoparticle, 2) preparation and successful filing of an Investigational New Drug application with the FDA, and 3) demonstrating in a first-in-human study that Pvs230D1 is a suitable antigenic target to generate transmission-blocking antibodies, using a safe formulation that induces sustained high antibody responses. Using our chemical conjugation platform, Pvs230D1 has been chemically conjugated to EPA and the conjugated nanoparticle enhanced immunogenicity compared to the monomer in mice. The antibodies raised against the conjugate reduced transmission of P. vivax to mosquitoes in the ex vivo membrane feeding assay. In FY18, a manufacturing campaign was initiated for the cGMP production of a Pvs230D1-EPA chemically conjugated vaccine for phase 1 human trials, with funds provided by OD, NIAID. The technical transfer process has proceeded according to project timelines. In FY2019, cGMP pilot-scale fermentation was successfully completed to produce a purification feedstock. In addition, the downstream purification process for cGMP operations was transferred successfully. The cGMP purification is scheduled for the end of FY2019. The technical transfer of the conjugation process is ongoing. As noted, due to the importance of strong durable antibody titers, adjuvant selection studies are ongoing in mice. In support of the IND filing, Pvs230D1M monoclonal antibody development and selection are ongoing as well. It is anticipated that an IND will be filed in FY2020 to assess the safety and immunogenicity of a Pvs230D1M-EPA conjugate vaccine followed by a later study to assess a controlled human malaria infection and transmission blocking late in FY2021. In FY2019, LMIV worked with collaborators from QIMR-B, Brisbane, Australia and with colleagues in OCRPRO, DCR, NIAID, to prepare content for the Biologics Master File that would allow controlled infections at the NIH CC of human volunteers with a blood stage inoculum of P. vivax. The inoculum will be provided by QIMR-B from cell banks they have established and used for controlled infections (called Induced Blood Stage Malaria or IBSM) of human subjects. Preparations are being made for an IBSM study at the NIH CC in FY 2020 that will generate P. vivax cell banks suitable for future IBSM studies and PvTBV vaccine efficacy trials.
| An, So Jung; Scaria, Puthupparampil V; Chen, Beth et al. (2018) Development of a bivalent conjugate vaccine candidate against malaria transmission and typhoid fever. Vaccine 36:2978-2984 |
| 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 |
| 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 : |
