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疟疾双价病毒载体疫苗可预防恶性疟原虫和间日疟原虫，并阻断寄生虫传播。

Malaria bivalent viral vectored vaccine protects against Plasmodium falciparum and vivax and blocks parasite transmission.

作者信息

Yamamoto Yutaro, Katayama Takuto, Fabbri Camila, Niwa Sora, Okuhara Daiki, Iyori Mitsuhiro, Hasyim Ammar A, Mizukami Hiroaki, Shida Hisatoshi, Lopes Stefanie, Yoshida Shigeto

机构信息

Laboratory of Vaccinology and Applied Immunology, Kanazawa University School of Pharmacy, Kanazawa University, Ishikawa, Japan.

Instituto Leônidas & Maria Deane-Fiocruz Amazônia, Laboratório de Diagnóstico e Controle e Doenças Infecciosas da Amazônia, Manaus, Amazonas, Brazil.

出版信息

NPJ Vaccines. 2025 Jul 26;10(1):171. doi: 10.1038/s41541-025-01229-3.

DOI:10.1038/s41541-025-01229-3
PMID:40715105
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12297270/
Abstract

Malaria remains a major infectious disease, with Plasmodium falciparum and Plasmodium vivax often co-endemic, requiring a dual-target vaccine for adequate control. We previously developed monovalent vaccines against P. falciparum or P. vivax using vaccinia virus LC16m8Δ (m8Δ) and adeno-associated virus type 1 (AAV1). Here, we demonstrate the efficacy of a novel bivalent malaria vaccine against P. falciparum and P. vivax. The m8Δ vaccine harbors two gene cassettes encoding Pfs25-PfCSP and Pvs25-PvCSP fusion proteins, while the AAV1 vaccine includes two recombinant AAV1s carrying one of these cassettes as a mixture. Heterologous m8Δ-prime and AAV1-boost immunization provided 70% protection against both PfCSP/Pb and PvCSP/Pb transgenic sporozoites. Moreover, a membrane feeding assay using P. vivax isolates from infected patients in the Brazilian Amazon showed 90% transmission-blocking efficacy. The bivalent vaccine outperformed monovalent combinations, maintaining immune responses for over 7 months, and shows promise for malaria control and elimination.

摘要

疟疾仍然是一种主要的传染病，恶性疟原虫和间日疟原虫常常共同流行，因此需要一种双靶点疫苗来实现充分防控。我们之前利用痘苗病毒LC16m8Δ（m8Δ）和1型腺相关病毒（AAV1）开发了针对恶性疟原虫或间日疟原虫的单价疫苗。在此，我们展示了一种新型双价疟疾疫苗针对恶性疟原虫和间日疟原虫的有效性。m8Δ疫苗含有两个编码Pfs25-PfCSP和Pvs25-PvCSP融合蛋白的基因盒，而AAV1疫苗则包含两种携带其中一个基因盒的重组AAV1作为混合物。异源m8Δ初免和AAV1加强免疫对PfCSP/Pb和PvCSP/Pb转基因子孢子均提供了70%的保护。此外，使用来自巴西亚马逊地区感染患者的间日疟原虫分离株进行的膜饲试验显示出90%的传播阻断效力。该双价疫苗优于单价组合疫苗，能将免疫反应维持7个月以上，有望用于疟疾的防控和消除。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/446e/12297270/0588bab24a61/41541_2025_1229_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/446e/12297270/53058b70f418/41541_2025_1229_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/446e/12297270/1ef48621fc2e/41541_2025_1229_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/446e/12297270/a2a1eca7cc7b/41541_2025_1229_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/446e/12297270/b255b479bcb2/41541_2025_1229_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/446e/12297270/bb306869b8a7/41541_2025_1229_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/446e/12297270/c97a90ec0e9c/41541_2025_1229_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/446e/12297270/0588bab24a61/41541_2025_1229_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/446e/12297270/53058b70f418/41541_2025_1229_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/446e/12297270/1ef48621fc2e/41541_2025_1229_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/446e/12297270/a2a1eca7cc7b/41541_2025_1229_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/446e/12297270/b255b479bcb2/41541_2025_1229_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/446e/12297270/bb306869b8a7/41541_2025_1229_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/446e/12297270/c97a90ec0e9c/41541_2025_1229_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/446e/12297270/0588bab24a61/41541_2025_1229_Fig7_HTML.jpg

相似文献

[1]
Malaria bivalent viral vectored vaccine protects against Plasmodium falciparum and vivax and blocks parasite transmission.

NPJ Vaccines. 2025-7-26

[2]
A two-dose viral-vectored multistage vaccine confers durable protection and transmission-blockade in a pre-clinical study.

Front Immunol. 2024

[3]
Adeno-associated virus-based malaria booster vaccine following attenuated replication-competent vaccinia virus LC16m8Δ priming.

Parasitol Int. 2023-2

[4]
Sterile protection and transmission blockade by a multistage anti-malarial vaccine in the pre-clinical study.

Front Immunol. 2022

[5]
Generation of a Transgenic Parasite Expressing Circumsporozoite Protein for Testing CSP-Based Malaria Vaccines in Non-Human Primates.

Vaccines (Basel). 2025-5-17

[6]
Adeno-Associated Virus as an Effective Malaria Booster Vaccine Following Adenovirus Priming.

Front Immunol. 2019-4-5

[7]
Vaccines for preventing malaria.

Cochrane Database Syst Rev. 2003

[8]
WITHDRAWN: Vaccines for preventing malaria.

Cochrane Database Syst Rev. 2007-7-18

[9]
Assessment of copy number variation in genes related to drug resistance in Plasmodium vivax and Plasmodium falciparum isolates from the Brazilian Amazon and a systematic review of the literature.

Malar J. 2017-4-19

[10]
Rapid diagnostic tests for diagnosing uncomplicated non-falciparum or Plasmodium vivax malaria in endemic countries.

Cochrane Database Syst Rev. 2014-12-18

本文引用的文献

[1]
WHO world malaria report 2024.

Lancet Microbe. 2025-2-6

[2]
A Head-to-Head Comparative Study of the Replication-Competent Vaccinia Virus and AAV1-Based Malaria Vaccine versus RTS,S/AS01 in Murine Models.

Vaccines (Basel). 2024-10-10

[3]
A two-dose viral-vectored multistage vaccine confers durable protection and transmission-blockade in a pre-clinical study.

Front Immunol. 2024

[4]
Structural and immunological differences in Plasmodium falciparum sexual stage transmission-blocking vaccines comprised of Pfs25-EPA nanoparticles.

NPJ Vaccines. 2023-4-15

[5]
Sterile protection and transmission blockade by a multistage anti-malarial vaccine in the pre-clinical study.

Front Immunol. 2022

[6]
The duration of protection against clinical malaria provided by the combination of seasonal RTS,S/AS01 vaccination and seasonal malaria chemoprevention versus either intervention given alone.

BMC Med. 2022-10-7

[7]
latent liver infection is characterized by persistent hypnozoites, hypnozoite-derived schizonts, and time-dependent efficacy of primaquine.

Mol Ther Methods Clin Dev. 2022-8-2

[8]
Adeno-associated virus-based malaria booster vaccine following attenuated replication-competent vaccinia virus LC16m8Δ priming.

Parasitol Int. 2023-2

[9]
Recent clinical trials inform the future for malaria vaccines.

Commun Med (Lond). 2021-8-25

[10]
Missed Plasmodium falciparum and Plasmodium vivax Mixed Infections in Ethiopia Threaten Malaria Elimination.

Am J Trop Med Hyg. 2021-11-30

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