A Viral-Vectored Multi-Stage Malaria Vaccine Regimen With Protective and Transmission-Blocking Efficacies

• Published in: Frontiers in immunology 2019-10, Vol.10, p.2412-2412
• Main Authors: Yusuf, Yenni, Yoshii, Tatsuya, Iyori, Mitsuhiro, Mizukami, Hiroaki, Fukumoto, Shinya, Yamamoto, Daisuke S, Emran, Talha Bin, Amelia, Fitri, Islam, Ashekul, Syafira, Intan, Yoshida, Shigeto
• Format: Article
• Language: English
• Subjects: adeno-associated virus; human adenovirus serotype 5; Immunology; multi-stage malaria vaccine; Pfs25; Plasmodium falciparum circumsporozoite protein; transmission-blocking
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2019.02412

Malaria parasites undergo several stages in their complex lifecycle. To achieve reductions in both the individual disease burden and malaria transmission within communities, a multi-stage malaria vaccine with high effectiveness and durability is a more efficacious strategy compared with a single-stage vaccine. Here, we generated viral-vectored vaccines based on human adenovirus type 5 (AdHu5) and adeno-associated virus serotype 1 (AAV1) expressing a fusion protein of the pre-erythrocytic stage circumsporozoite protein (PfCSP) and the transmission-blocking sexual stage P25 protein (Pfs25). A two-dose heterologous AdHu5-prime/AAV1-boost immunization regimen proved to be highly effective for both full protection and transmission-blocking activity against transgenic parasites expressing the corresponding antigens in mice. Remarkably, the immunization regimen induced antibody responses to both PfCSP and Pfs25 for over 9 months after the boosting and also maintained high levels of transmission-reducing activity (TRA: >99%) during that period, as evaluated by a direct feeding assay. If similar efficacies on can be shown following vaccination of humans, we propose that this multi-stage malaria vaccine regimen will be a powerful tool for malaria control, providing greater overall protection and cost-effectiveness than single-stage vaccines.