A multi-stage malaria vaccine candidate targeting both transmission and asexual parasite life-cycle stages

Effective control and eventual eradication of malaria drives the imperative need for clinical development of a malaria vaccine. Asexual parasite forms are responsible for clinical disease and death while apathogenic gametocytes are responsible for transmission from man to mosquito. Vaccines that combine antigens from both stages may provide direct protection and indirect benefit by reducing the force of infection. We constructed a chimeric antigen composed of a fragment of the Plasmodium falciparum (Pf) glutamate-rich protein fused in frame to a correctly folded fragment of Pfs48/45. The chimera was produced in Lactococcus lactis and induced robust antibody responses in rodents to the individual components. Specific antibodies showed strong transmission blocking activity against multiple Pf-strains in the standard membrane feeding assay and functional activity against asexual stages in the antibody dependent cellular inhibition assay. The combined data provide a strong rationale for entering the next phase of clinical grade production and testing.