Sterile protection and transmission blockade by a multistage anti-malarial vaccine in the pre-clinical study
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 b...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1005476/full |
| _version_ | 1811258175787106304 |
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| author | Mitsuhiro Iyori Andrew M. Blagborough Tetsushi Mizuno Yu-ichi Abe Mio Nagaoka Naoto Hori Iroha Yamagoshi Dari F. Da William F. Gregory Ammar A. Hasyim Yutaro Yamamoto Akihiko Sakamoto Kunitaka Yoshida Hiroaki Mizukami Hisatoshi Shida Shigeto Yoshida |
| author_facet | Mitsuhiro Iyori Andrew M. Blagborough Tetsushi Mizuno Yu-ichi Abe Mio Nagaoka Naoto Hori Iroha Yamagoshi Dari F. Da William F. Gregory Ammar A. Hasyim Yutaro Yamamoto Akihiko Sakamoto Kunitaka Yoshida Hiroaki Mizukami Hisatoshi Shida Shigeto Yoshida |
| author_sort | Mitsuhiro Iyori |
| collection | DOAJ |
| description | 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, LC16m8Δ (m8Δ), 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 m8Δ-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 m8Δ/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. |
| first_indexed | 2024-04-12T18:09:12Z |
| format | Article |
| id | doaj.art-633da31b4040440cbce04c0fe0254da1 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-12T18:09:12Z |
| publishDate | 2022-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-633da31b4040440cbce04c0fe0254da12022-12-22T03:21:53ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-09-011310.3389/fimmu.2022.10054761005476Sterile protection and transmission blockade by a multistage anti-malarial vaccine in the pre-clinical studyMitsuhiro Iyori0Andrew M. Blagborough1Tetsushi Mizuno2Yu-ichi Abe3Mio Nagaoka4Naoto Hori5Iroha Yamagoshi6Dari F. Da7William F. Gregory8Ammar A. Hasyim9Yutaro Yamamoto10Akihiko Sakamoto11Kunitaka Yoshida12Hiroaki Mizukami13Hisatoshi Shida14Shigeto Yoshida15Laboratory of Vaccinology and Applied Immunology, Kanazawa University School of Pharmacy, Kanazawa University, Ishikawa, JapanDepartment of Pathology, University of Cambridge, Cambridge, United KingdomDepartment of Parasitology, Graduate School of Medical Sciences, Kanazawa University, Ishikawa, JapanLaboratory of Vaccinology and Applied Immunology, Kanazawa University School of Pharmacy, Kanazawa University, Ishikawa, JapanLaboratory of Vaccinology and Applied Immunology, Kanazawa University School of Pharmacy, Kanazawa University, Ishikawa, JapanLaboratory of Vaccinology and Applied Immunology, Kanazawa University School of Pharmacy, Kanazawa University, Ishikawa, JapanLaboratory of Vaccinology and Applied Immunology, Kanazawa University School of Pharmacy, Kanazawa University, Ishikawa, JapanDépartement de Biologie Médicale et Santé Publique, Unité Paludisme et Maladies Tropicales Négligées, Institut de Recherche en Sciences de la Santé, Bobo-Dioulasso, Burkina FasoDepartment of Pathology, University of Cambridge, Cambridge, United KingdomLaboratory of Vaccinology and Applied Immunology, Kanazawa University School of Pharmacy, Kanazawa University, Ishikawa, JapanLaboratory of Vaccinology and Applied Immunology, Kanazawa University School of Pharmacy, Kanazawa University, Ishikawa, JapanLaboratory of Vaccinology and Applied Immunology, Kanazawa University School of Pharmacy, Kanazawa University, Ishikawa, JapanLaboratory of Vaccinology and Applied Immunology, Kanazawa University School of Pharmacy, Kanazawa University, Ishikawa, JapanDivision of Gene Therapy, Jichi Medical University, Tochigi, JapanInstitute for Genetic Medicine, Hokkaido University, Hokkaido, JapanLaboratory of Vaccinology and Applied Immunology, Kanazawa University School of Pharmacy, Kanazawa University, Ishikawa, JapanThe 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, LC16m8Δ (m8Δ), 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 m8Δ-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 m8Δ/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.https://www.frontiersin.org/articles/10.3389/fimmu.2022.1005476/fullmalariavaccineplasmodium falciparumPfCSPPfs25LC16m8Δ |
| spellingShingle | Mitsuhiro Iyori Andrew M. Blagborough Tetsushi Mizuno Yu-ichi Abe Mio Nagaoka Naoto Hori Iroha Yamagoshi Dari F. Da William F. Gregory Ammar A. Hasyim Yutaro Yamamoto Akihiko Sakamoto Kunitaka Yoshida Hiroaki Mizukami Hisatoshi Shida Shigeto Yoshida Sterile protection and transmission blockade by a multistage anti-malarial vaccine in the pre-clinical study Frontiers in Immunology malaria vaccine plasmodium falciparum PfCSP Pfs25 LC16m8Δ |
| title | Sterile protection and transmission blockade by a multistage anti-malarial vaccine in the pre-clinical study |
| title_full | Sterile protection and transmission blockade by a multistage anti-malarial vaccine in the pre-clinical study |
| title_fullStr | Sterile protection and transmission blockade by a multistage anti-malarial vaccine in the pre-clinical study |
| title_full_unstemmed | Sterile protection and transmission blockade by a multistage anti-malarial vaccine in the pre-clinical study |
| title_short | Sterile protection and transmission blockade by a multistage anti-malarial vaccine in the pre-clinical study |
| title_sort | sterile protection and transmission blockade by a multistage anti malarial vaccine in the pre clinical study |
| topic | malaria vaccine plasmodium falciparum PfCSP Pfs25 LC16m8Δ |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1005476/full |
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