Stability and potency of the Plasmodium falciparum MSP1-19/AMA-1(III) chimeric vaccine candidate with Montanide ISA720 adjuvant.

The Plasmodium falciparum AMA-1(III) and MSP1-19 proteins have been expressed as a chimera (PfCP-2.9), adjuvanted with Montanide ISA720 and developed as a vaccine candidate tested in human. The PfCP-2.9 protein contains 18 cysteine residues that form nine intramolecular disulfide bonds. The protective immune responses induced by the chimeric protein were dependent on its disulfide bond-based conformation. In this study, we developed a sandwich ELISA to assess the nature of the protein in the emulsion over time (6, 12 and 18 months). Our results showed that the OD(450) values corresponding to vaccine storages were within the 95% confidence interval, indicating that the conformation of the protein in the emulsion stored for up to 18 months at 4 degrees C was unchanged. Furthermore, no protein degradation was detected by Coomassie blue, silver staining, and Western blot analysis for samples stored at 4 degrees C for up to 2 years. Although some protein aggregation was observed in the emulsion preparations, these aggregates were only a small percentage of the total protein in the sample (7.6%). Moreover, the protein multimers maintained their conformational epitope. The potency assay of the formulation showed no significant differences in ED(50) values (50% effective dose for achieving seroconversion) between fresh vaccine formulations (ED(50)=0.057+/-0.024 microg) and formulations stored for up to 6 (ED(50)=0.046 microg) or 12 months (ED(50)=0.040 microg). Importantly, the immune sera of rabbits immunized with formulations stored for 0, 3, 6, 9 and 12 months effectively inhibited parasite growth in vitro at similar levels. These data indicated that the vaccine emulsion was stable over long periods of storage and maintained both its physical and biological properties.

Xue X ，Ding F ，Zhang Q ，Pan X ，Qu L ，Pan W ... -  《-》

A human phase 1 vaccine clinical trial of the Plasmodium falciparum malaria vaccine candidate apical membrane antigen 1 in Montanide ISA720 adjuvant.

Saul A ，Lawrence G ，Allworth A ，Elliott S ，Anderson K ，Rzepczyk C ，Martin LB ，Taylor D ，Eisen DP ，Irving DO ，Pye D ，Crewther PE ，Hodder AN ，Murphy VJ ，Anders RF ... -  《VACCINE》

Immunogenicity of a chimeric Plasmodium falciparum merozoite surface protein vaccine in Aotus monkeys.

Burns JM Jr ，Miura K ，Sullivan J ，Long CA ，Barnwell JW ... -  《MALARIA JOURNAL》

Immunogenicity of a recombinant malaria vaccine candidate, domain I+II of AMA-1 ectodomain, from Indian P. falciparum alleles.

Lalitha PV ，Biswas S ，Pillai CR ，Saxena RK ... -  《VACCINE》

Adenovectors induce functional antibodies capable of potent inhibition of blood stage malaria parasite growth.

An effective malaria vaccine remains a global health priority. Recombinant adenoviruses are a promising vaccine platform, and Plasmodium falciparum apical membrane antigen 1 (AMA1) and merozoite surface protein 1-42 (MSP1(42)) are leading blood stage vaccine candidates. We evaluated the importance of surface antigen localization and glycosylation on the immunogenicity of adenovector delivered AMA1 and MSP1(42) and assessed the ability of these vaccines to induce functional antibody responses capable of inhibiting parasite growth in vitro. Adenovector delivery induced unprecedented levels of biologically active antibodies in rabbits as indicated by the parasite growth inhibition assay. These responses were as potent as published results using any other vaccine system, including recombinant protein in adjuvant. The cell surface associated and glycosylated forms of AMA1 and MSP1(42) elicited 99% and 60% inhibition of parasite growth, respectively. Antigens that were expressed at the cell surface and glycosylated were much better than intracellular antigens at inducing antibody responses. Good T cell responses were observed for all forms of AMA1 and MSP1(42). Antigen-specific antibody responses, but typically not T cell responses, were boosted by a second administration of adenovector. These data highlight the importance of rational vaccine design and support the advancement of adenovector delivery technology for a malaria vaccine.

Bruder JT ，Stefaniak ME ，Patterson NB ，Chen P ，Konovalova S ，Limbach K ，Campo JJ ，Ettyreddy D ，Li S ，Dubovsky F ，Richie TL ，King CR ，Long CA ，Doolan DL ... -  《-》