Comparative Assessment of Transmission-Blocking Vaccine Candidates against Plasmodium falciparum

• DOI: 10.1038/srep11193
• Publication Date: 2015-06-11T10:54:20Z
• Authors: M. C. Kapulu; D. F. Da; K. Miura; Y Li; A. M. Blagborough; T. S. Churcher; D. Nikolaeva; A. R. Williams; A. L. Goodman; I. Sangare; A. V. Turner; M. G. Cottingham; A. Nicosia; U. Straschil; T. Tsuboi; S. C. Gilbert; Carole A. Long; R. E. Sinden; S. J. Draper; A. V. S. Hill; A. Cohuet; S. Biswas
• Keywords: ADJUVANT VACCINES; Falciparum; Animals; Anopheles; Antibodies, Protozoan; Antigens, Protozoan; Culicidae; Disease Models, Animal; Genetic Vectors; Humans; Immunization; Immunoglobulin G; Malaria Vaccines; Malaria, Falciparum; Mice; Plasmodium falciparum; Recombinant Fusion Proteins; Multidisciplinary; Recombinant Fusion Proteins; CELL-FREE SYSTEM; Genetic Vectors; Plasmodium falciparum; 610; PROTEIN; Antibodies, Protozoan; Antigens, Protozoan; Antibodies; Article; MEMBRANE-FEEDING ASSAY; Mice; 03 medical and health sciences; SURFACE-ANTIGEN PFS230; Anopheles; Malaria Vaccines; Animals; Humans; SEXUAL-STAGE; Antigens; Malaria, Falciparum; 0303 health sciences; Science & Technology; MALARIA TRANSMISSION; Multidisciplinary; Animal; Malaria; 3. Good health; Multidisciplinary Sciences; Disease Models, Animal; Culicidae; Immunoglobulin G; ANTIBODIES; Protozoan; Disease Models; Science & Technology - Other Topics; Immunization; VIVAX MALARIA; RESPONSES

AbstractMalaria transmission-blocking vaccines (TBVs) target the development of Plasmodium parasites within the mosquito, with the aim of preventing malaria transmission from one infected individual to another. Different vaccine platforms, mainly protein-in-adjuvant formulations delivering the leading candidate antigens, have been developed independently and have reported varied transmission-blocking activities (TBA). Here, recombinant chimpanzee adenovirus 63, ChAd63 and modified vaccinia virus Ankara, MVA, expressing AgAPN1, Pfs230-C, Pfs25 and Pfs48/45 were generated. Antibody responses primed individually against all antigens by ChAd63 immunization in BALB/c mice were boosted by the administration of MVA expressing the same antigen. These antibodies exhibited a hierarchy of inhibitory activity against the NF54 laboratory strain of P. falciparum in Anopheles stephensi mosquitoes using the standard membrane feeding assay (SMFA), with anti-Pfs230-C and anti-Pfs25 antibodies giving complete blockade. The observed rank order of inhibition was replicated against P. falciparum African field isolates in A. gambiae in direct membrane feeding assays (DMFA). TBA achieved was IgG concentration dependent. This study provides the first head-to-head comparative analysis of leading antigens using two different parasite sources in two different vector species and can be used to guide selection of TBVs for future clinical development using the viral-vectored delivery platform.