Expanding the breadth, magnitude, and durability of PfSPZ vaccines by creating multi-strain vaccines, designer hybrid and genetically altered parasite vaccines and use of a unique adjuvant
To identify, characterize and optimize PfSPZ production from E. African and Asian strains of P. falciparum.
Plasmodium falciparum (Pf) sporozoite (SPZ)-based vaccines have shown excellent safety and vaccine efficacy (VE) in more than 25 clinical trials in Africa, Europe, and the US; Phase 3 assessment will begin in mid 2020. Our goal during the next decade is to develop, license, and deploy next generation PfSPZ vaccines with increased breadth, magnitude, and/or durability of VE and decreased cost of goods. The 1st and 2nd generation aseptic, purified, cryopreserved PfSPZ vaccines, whether radiation-, chemo-, or genetically-attenuated are composed of Pf of the West (W.) African strain of Pf, NF54. In general East (E.) African strains of Pf are more distant genetically from NF54 than are W. African strains, and Asian strains are much more distant genetically from NF54 than are any African Pf strains. Thus, it is possible that immunizing with an E. African strain in E. Africa will be more protective than immunizing with the W. African strain, NF54. Likewise, immunizing with an Asian strain of Pf in Asia will likely be more protective than immunizing with a W. African strain like NF54.
We propose to increase the magnitude/potency of the immune response to any dose of PfSPZ by selecting for PfSPZ that are more infective to hepatocytes and by creating through genetic alteration, late arresting replication component PfSPZ that express many more antigens and more of each antigen than do current early arresting radiation- and genetically-attenuated PfSPZ. Adjuvants have often provided the most direct route to increasing the durability of vaccines. We have identified a glycolipid adjuvant that increases the potency and durability of murine malaria SPZ vaccines. In this project we will determine the impact of this adjuvant on the immunogenicity of the hybrid and late arresting strains we develop by assessing in non-human primates.