Authors

T Mizuno²; AM Blagborough¹; M Niikura³; AA Hasyim⁴; M Iyori⁴; Y Yamamoto⁴; A Sakamoto⁴; H Mizukami⁵; H Shida⁶; S Yoshida⁴;  ¹ Department of Pathology, University of Cambridge, UK;  ² Department of Global Infectious Diseases, Kanazawa University, Japan;  ³ Department of Infectious Diseases, Kyorin University, Japan;  ⁴ Laboratory of Vaccinology and Applied Immunology, Kanazawa University, Japan;  ⁵ Division of Gene Therapy, Jichi Medical University, Japan;  ⁶ Institute for Genetic Medicine, Hokkaido University, Japan

Discussion

The Malaria Vaccine Technology Roadmap 2013 (World Health Organization) aims to develop safe and effective vaccines by 2030. It targets at least 75% protective efficacy. Recently, we’ve established a highly effective multistage vaccine against Plasmodium falciparum. This heterologous prime-boost viral-vectored vaccine induces both humoral and cellular immune responses effectively and durable. This notable vaccine is targeting multi-stage in P. falciparum life cycles. The vaccine encodes both a pre-erythrocytic stage antigen circumsporozoite protein (PfCSP) and one sexual stage antigens s25 (Pfs25). The combination between the pre-erythrocytic vaccine (PEV) effect and transmission-blocking vaccine (TBV) effect brings the synergy to enhance the vaccine more potent in malaria prevention than single antigen target strategy. In this study, we evaluated both PE and TB efficacies of our newly-developed vaccine in a rodent model. As a result, our vaccine showed 100% protection as PEV against PfCSP-transgenic P. berghei sporozoites and more than 90% oocyst reduction in mosquito midgut as TBV against Pfs25-transgenic P. berghei. Next, we evaluated its synergy of TBV+PEV on a double transgenic P. berghei expressing both PfCSP and Pfs25. We performed the assay in conditions that weaken our vaccine effect to measure the benefit of synergy. As a result, while the individual efficacy decreased to about 50% in TBV and about 60% in PEV respectively, the synergy of TBV+PEV remained over 90%. These findings propose the potential of our vaccine as a ”next-generation malaria vaccine” to achieve the landmark goals of the malaria vaccine technology roadmap.