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Malaria transmission blocking (TB) vaccines (TBVs) directed against proteins expressed on the sexual stages of Plasmodium parasites are a potentially effective means to reduce transmission. Antibodies induced by TBVs block parasite development in the mosquito, and thus inhibit transmission to further human hosts. The ookinete surface protein P25 is a primary target for TBV development. Recently, transient expression in plants using hybrid viral vectors has demonstrated potential as a strategy for cost-effective and scalable production of recombinant vaccines. Using a plant virus-based expression system, we produced recombinant P25 protein of Plasmodium vivax (Pvs25) in Nicotiana benthamiana fused to a modified lichenase carrier protein. This candidate vaccine, Pvs25-FhCMB, was purified, characterized and evaluated for immunogenicity and efficacy using multiple adjuvants in a transgenic rodent model. An in vivo TB effect of up to a 65% reduction in intensity and 54% reduction in prevalence was observed using Abisco-100 adjuvant. The ability of this immunogen to induce a TB response was additionally combined with heterologous prime-boost vaccination with viral vectors expressing Pvs25. Significant blockade was observed when combining both platforms, achieving a 74% and 68% reduction in intensity and prevalence, respectively. This observation was confirmed by direct membrane feeding on field P. vivax samples, resulting in reductions in intensity/prevalence of 85.3% and 25.5%. These data demonstrate the potential of this vaccine candidate and support the feasibility of expressing Plasmodium antigens in a plant-based system for the production of TBVs, while demonstrating the potential advantages of combining multiple vaccine delivery systems to maximize efficacy.

Original publication

DOI

10.1016/j.vaccine.2016.05.007

Type

Journal article

Journal

Vaccine

Publication Date

14/06/2016

Volume

34

Pages

3252 - 3259

Keywords

Malaria, Plant-produced antigen, Plasmodium, Pvs25, Subunit vaccine, Transmission blocking vaccine, Adjuvants, Immunologic, Animals, Female, Immunization, Secondary, Malaria Vaccines, Malaria, Vivax, Mice, Inbred BALB C, Plants, Genetically Modified, Plasmodium vivax, Protozoan Proteins, Recombinant Proteins, Tobacco, Vaccines, Subunit, Vaccines, Synthetic