Development of Pre-Erythrocytic Malaria Vaccines and antibodies

National Institute Of Allergy And Infectious Diseases

Investigators

Linked publications, trials & patents

Abstract

The major discovery this year are as follows. 1. Completed immune and efficacy analysis of a phase II clinical trial in Kenya in 5-12 month infants to assess whether irradiated PfSPZ given by the IV route is safe, and confers durable immunity and protection against natural exposure. 2. Increased the half-life of mAb CIS43 by introducing an LS mutation in the Fc region. CIS43LS was shown to have comparable protection in vivo as CIS43 but have significantly longer half-life in non-human primates. 2. Initiated a Phase I clinical trial for mAB CIS 43LS against the junctional region of PfCSP for safety, pharmacokinetics and protection against controlled human malaria infection. 4. Isolated a new human mAb, L9, which defined a new distinct epitope comprising the minor and major repeats of PfCSP. 5. Comparative analysis of the in vivo potency of L9 against a number of human mAbs against CSP. Elucidated in vivo mechanisms of these antibodies demonstrating that several of them limit infection in the liver. 6. Developed in vivo imaging techniques to model the interaction between antibodies and sporozoites in mice. 7. Completed a Phase 1 safety and efficacy study with L9LS in humans. Data showed high level protection at low doses by SC or IV route. 8. Initiated two Phase 2 clinical trials in Mali and Kenya in infants and children to assess the safety and efficacy of L9LS against seasonal and perennial infection.