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| Content Provider | frontiers |
|---|---|
| Author | Iyori, Mitsuhiro Blagborough, Andrew M. Mizuno, Tetsushi Abe, Yu-ichi Nagaoka, Mio Hori, Naoto Yamagoshi, Iroha Da, Dari F. Gregory, William F. Hasyim, Ammar A. Yamamoto, Yutaro Sakamoto, Akihiko Yoshida, Kunitaka Mizukami, Hiroaki Shida, Hisatoshi Yoshida, Shigeto |
| Abstract | The Malaria Vaccine Technology Roadmap 2013 (World Health Organization) aims to develop safe and effective vaccines by 2030 that will offer at least 75% protective efficacy against clinical malaria and reduce parasite transmission. Here, we demonstrate a highly effective multistage vaccine against both the pre-erythrocytic and sexual stages of Plasmodium falciparum that protects and reduces transmission in a murine model. The vaccine is based on a viral-vectored vaccine platform, comprising a highly-attenuated vaccinia virus strain, LC16m8∆ (m8∆), a genetically stable variant of a licensed and highly effective Japanese smallpox vaccine LC16m8, and an adeno-associated virus (AAV), a viral vector for human gene therapy. The genes encoding P. falciparum circumsporozoite protein (PfCSP) and the ookinete protein P25 (Pfs25) are expressed as a Pfs25–PfCSP fusion protein, and the heterologous m8∆-prime/AAV-boost immunization regimen in mice provided both 100% protection against PfCSP-transgenic P. berghei sporozoites and up to 100% transmission blocking efficacy, as determined by a direct membrane feeding assay using parasites from P. falciparum-positive, naturally-infected donors from endemic settings. Remarkably, the persistence of vaccine-induced immune responses were over 7 months and additionally provided complete protection against repeated parasite challenge in a murine model. We propose that application of the m8∆/AAV malaria multistage vaccine platform has the potential to contribute to the landmark goals of the malaria vaccine technology roadmap, to achieve life-long sterile protection and high-level transmission blocking efficacy. |
| ISSN | 16643224 |
| DOI | 10.3389/fimmu.2022.1005476 |
| Volume Number | 13 |
| Journal | Frontiers in Immunology |
| Language | English |
| Publisher Date | 2022-09-29 |
| Access Restriction | Open |
| Subject Keyword | Vaccine Pfs25 Malaria PFCSP AAV (Adeno-associated virus) Plasmodium falciparum LC16m8∆ |
| Content Type | Text |
| Resource Type | Article |
| Subject | Immunology and Allergy Immunology |
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