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Accelerated prime-and-trap vaccine regimen in mice using repRNA-based CSP malaria vaccine.

作者信息

MacMillen Zachary, Hatzakis Kiara, Simpson Adrian, Shears Melanie J, Watson Felicia, Erasmus Jesse H, Khandhar Amit P, Wilder Brandon, Murphy Sean C, Reed Steven G, Davie James W, Avril Marion

机构信息

MalarVx, Inc 1551 Eastlake Ave E, Suite 100, Seattle, WA, 98102, USA.

HDT Bio, 1150 Eastlake Ave E, Suite 200A, Seattle, WA, 98109, USA.

出版信息

NPJ Vaccines. 2024 Jan 10;9(1):12. doi: 10.1038/s41541-023-00799-4.


DOI:10.1038/s41541-023-00799-4
PMID:38200025
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10781674/
Abstract

Malaria, caused by Plasmodium parasites, remains one of the most devastating infectious diseases worldwide, despite control efforts to lower morbidity and mortality. Both advanced candidate vaccines, RTS,S and R21, are subunit (SU) vaccines that target a single Plasmodium falciparum (Pf) pre-erythrocytic (PE) sporozoite (spz) surface protein known as circumsporozoite (CS). These vaccines induce humoral immunity but fail to elicit CD8 + T-cell responses sufficient for long-term protection. In contrast, whole-organism (WO) vaccines, such as Radiation Attenuated Sporozoites (RAS), achieved sterile protection but require a series of intravenous doses administered in multiple clinic visits. Moreover, these WO vaccines must be produced in mosquitos, a burdensome process that severely limits their availability. To reduce reliance on WO while maintaining protection via both antibodies and Trm responses, we have developed an accelerated vaccination regimen that combines two distinct agents in a prime-and-trap strategy. The priming dose is a single dose of self-replicating RNA encoding the full-length P. yoelii CS protein, delivered via an advanced cationic nanocarrier (LION). The trapping dose consists of one dose of WO RAS. Our vaccine induces a strong immune response when administered in an accelerated regimen, i.e., either 5-day or same-day immunization. Additionally, mice after same-day immunization showed a 2-day delay of blood patency with 90% sterile protection against a 3-week spz challenge. The same-day regimen also induced durable 70% sterile protection against a 2-month spz challenge. Our approach presents a clear path to late-stage preclinical and clinical testing of dose-sparing, same-day regimens that can confer sterilizing protection against malaria.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/105f/10781674/7e3eb2cb69c5/41541_2023_799_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/105f/10781674/7e3eb2cb69c5/41541_2023_799_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/105f/10781674/7e3eb2cb69c5/41541_2023_799_Fig1_HTML.jpg

相似文献

[1]
Accelerated prime-and-trap vaccine regimen in mice using repRNA-based CSP malaria vaccine.

NPJ Vaccines. 2024-1-10

[2]
Accelerated prime-and-trap vaccine regimen in mice using repRNA-based CSP malaria vaccine.

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[3]
Accelerated prime-and-trap vaccine regimen in mice using repRNA-based CSP malaria vaccine.

bioRxiv. 2023-5-23

[4]
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[5]
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[6]
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[7]
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[8]
Artesunate versus chloroquine infection-treatment-vaccination defines stage-specific immune responses associated with prolonged sterile protection against both pre-erythrocytic and erythrocytic Plasmodium yoelii infection.

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[9]
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[10]
A three-antigen Plasmodium falciparum DNA prime-Adenovirus boost malaria vaccine regimen is superior to a two-antigen regimen and protects against controlled human malaria infection in healthy malaria-naïve adults.

PLoS One. 2021

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[1]
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NPJ Vaccines. 2025-9-2

[2]
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J Hematol Oncol. 2025-4-17

[3]
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Nat Commun. 2025-1-14

[4]
Preclinical development of lyophilized self-replicating RNA vaccines for COVID-19 and malaria with improved long-term thermostability.

J Control Release. 2025-1-10

[5]
mRNA vaccines for infectious diseases - advances, challenges and opportunities.

Nat Rev Drug Discov. 2024-11

[6]
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Front Pharmacol. 2024-6-26

[7]
Immunogenicity, Efficacy, and Safety of a Novel Synthetic Microparticle Pre-Erythrocytic Malaria Vaccine in Multiple Host Species.

Vaccines (Basel). 2023-11-30

本文引用的文献

[1]
A localizing nanocarrier formulation enables multi-target immune responses to multivalent replicating RNA with limited systemic inflammation.

Mol Ther. 2023-8-2

[2]
Memory CD8+ T cell-mediated protection against liver-stage malaria.

Immunol Rev. 2023-7

[3]
An RNA-Based Vaccine Platform for Use against .

Vaccines (Basel). 2023-1-5

[4]
mRNA-LNP expressing PfCSP and Pfs25 vaccine candidates targeting infection and transmission of Plasmodium falciparum.

NPJ Vaccines. 2022-12-1

[5]
A genetically engineered parasite vaccine provides protection from controlled human malaria infection.

Sci Transl Med. 2022-8-24

[6]
PfSPZ-CVac malaria vaccine demonstrates safety among malaria-experienced adults: A randomized, controlled phase 1 trial.

EClinicalMedicine. 2022-7-30

[7]
Replicating RNA vaccination elicits an unexpected immune response that efficiently protects mice against lethal Crimean-Congo hemorrhagic fever virus challenge.

EBioMedicine. 2022-8

[8]
Cryopreserved Sporozoites with and without the Glycolipid Adjuvant 7DW8-5 Protect in Prime-and-Trap Malaria Vaccination.

Am J Trop Med Hyg. 2022-2-28

[9]
Protective effects of combining monoclonal antibodies and vaccines against the Plasmodium falciparum circumsporozoite protein.

PLoS Pathog. 2021-12

[10]
Safety and efficacy of a three-dose regimen of Plasmodium falciparum sporozoite vaccine in adults during an intense malaria transmission season in Mali: a randomised, controlled phase 1 trial.

Lancet Infect Dis. 2022-3

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