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- Title
A Viral-Vectored Multi-Stage Malaria Vaccine Regimen With Protective and Transmission-Blocking Efficacies.
- 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
- Abstract
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 Plasmodium falciparum 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 P. berghei parasites expressing the corresponding P. falciparum 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 P. falciparum 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.
- Subjects
MALARIA vaccines; ADENO-associated virus; CIRCUMSPOROZOITE protein; VACCINE effectiveness; CHIMERIC proteins
- Publication
Frontiers in Immunology, 2019, p1
- ISSN
1664-3224
- Publication type
Article
- DOI
10.3389/fimmu.2019.02412