Adaptive clinical trials of three PfSPZ products for development of a whole sporozoite vaccine that prevents Plasmodium falciparum infection, disease and transmission

Abstract

An ideal, single stage vaccine for elimination of Plasmodium falciparum (Pf) would prevent infection at the pre-erythrocytic stage of the life cycle, thereby preventing all Pf-caused disease and Pf transmission. The only approach to immunization that induces > 90% protection against nfection that is sustained for at least 10-28 months, is immunization by mosquito bite with whole Pf sporozoites (SPZ) of two types. The frst, radiation-attenuated PfSPZ, invades hepatoctyes and expresses new proteins, but cannot replicate. The second type fully develops in hepatocytes, producing tens of thousands of merozoites that invade erythrocytes, but cannot fully develop within erythrocytes, because the parasites are killed by chloroquine taken by during immunization. Sanaria was founded to develop PfSPZ vaccines. The 1st vaccine is based on radiation attenuated PfSPZ. The frst task accomplished was production of PfSPZ that met regulatory and cost of goods requirements. PfSPZ Vaccine comprises radiation attenuated, aseptic, purifed, cryopreserved PfSPZ. In the 1st clinical trial in 80 volunteers it was safe, and well tolerated However, it was sub-optimally immunogenic and protective due to neffcient administration. A 2nd product, PfSPZ Challenge, comprises non-rradiated, fully infectious PfSPZ. PfSPZ Challenge infected volunteers after ntradermal administration by needle and syringe. However, administration was not optimally effcient. A 3rd product, PfSPZ-CVac, comprises PfSPZ Challenge administered to volunteers while receiving chloroquine chemoprophylaxis. Assessment of these three products in interactive and adaptive clinical trials will facilitate progress toward optimizing administration and dosage regimen of all three whole PfSPZ products, as well as those developed in the future from genetically altered parasites, thereby speeding licensure of one or more PfSPZ-based vaccines. In 2011-2012 we will execute clinical trials of all three PfSPZ products at multiple clinical trials centers in N. America, Europe, and Africa. Plans and progress will be described.