Clinical development of Plasmodium falciparum malaria vaccines

Malaria remains a major threat to the lives of more than 3 billion people worldwide and there is a pressing and, as yet, unmet need for an effective vaccine that provides a high degree of sustained protection. Despite 3 decades of clinical testing of a substantial number of (recombinant) sub‐unit vaccines, only modest protection has been achieved so far, consequently renewing a strong interest in whole organism malaria vaccine approaches. Induction of complete protective immunity in humans has only been achieved by immunization with live, attenuated Plasmodium parasites that invade but then completely arrest in the liver.
 
From its discovery platform for clinical malaria vaccine development, Radboudumc has been able to generate 3 candidate vaccines for clinical testing in phase 1 trials:

• Radboudumc and Leiden UMC have pioneered the generation of the first in human patented Genetically Attenuated Parasite vaccine (GA-1) where two genes have been deleted to obtain complete life-cycle arrest in the liver. The US biotech Sanaria Inc. has purified, vialed and cryopreserved GA-1. Clinical safety study followed by a Controlled Human Malaria infection has started in 2017.
• Radboudumc and ErasmusMC are partnering in the clinical evaluation of PbVac generated in collaboration with MIM, Lisbon (ES). The is a genetically modified murine Plasmodium berghei parasite expressing the major Plasmodium falciparum vaccine target protein CSP. Safety and efficacy studies have started in 2017 and results are expected in 2018.
• Radboudumc has developed a patented Pfs48/45 protein vaccine in collaboration with SSI (DK) aimed to block transmission of malaria and considered essential for malaria elimination. Preclinical cGMP purification processes are in place and optimal formulation is currently pursued. A clinical trial is planned at Radboudumc early 2019.