Transmission blocking potency and immunogenicity of a plant-produced Pvs25-based subunit vaccine against Plasmodium vivax

A.M Blagborough,K Musiychuk,H Bi,R.M Jones,J.A Chichester,S Streatfield,K.A Sala,S.E Zakutansky,L.M Upton,R.E Sinden,I Brian,S Biswas,J Sattabonkot,V Yusibov

doi:10.1016/j.vaccine.2016.05.007

Abstract

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.

Highlights

Malaria is a global disease caused by parasites of the genus Plasmodium
We examined efficacy of this candidate vaccine by performing a head-to-head comparison of induced transmission blocking (TB) potency following mouse immunization with recombinant Pvs25-FhCMB in the presence of two clinically relevant adjuvants: Alhydrogel, a common aluminium hydroxide wet gel suspension, and Abisco-100, a non-toxic saponin-based adjuvant, and compared these to immunization with a lead adenoviral vaccine platform
Future control of malaria will require a multidimensional approach. Both the WHO and the Malaria Eradication Research Agenda have previously set as a core goal for any malaria vaccine program the need to reduce transmission and morbidity [43]

Summary

Introduction

Malaria is a global disease caused by parasites of the genus Plasmodium. An estimated 207 million cases of malaria are reported annually, causing approximately 627,000 deaths [1,2]. Of the five species of malaria parasites that infect humans, Plasmodium falciparum and Plasmodium vivax lead to the greatest burden of disease. While P. falciparum is responsible for the majority of malaria-linked deaths, P. vivax can cause relapses months after the first infection [4] caused by hypnozoites, and require specialized treatment, e.g. primaquine [2,3,4]. P. vivax is the most widely distributed human malaria parasite, with 2.5 billion people at risk of infection, and 80−300 million cases per annum [1,3]. Multiple factors, including the appearance of chloroquine-resistant P. vivax [5], lack of practical alternatives to primaquine, combined with increasing global temperatures [6,7], have raised concerns related to increased risks of P. vivax-induced disease

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