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从杜氏利什曼原虫生产利什曼菌素皮肤试验抗原，以备将来在野外重新引入。

Production of leishmanin skin test antigen from Leishmania donovani for future reintroduction in the field.

机构信息

Division of Emerging and Transfusion Transmitted Diseases, CBER, FDA, Silver Spring, MD, USA.

Department of Parasitology, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Nagasaki, Japan.

出版信息

Nat Commun. 2023 Nov 2;14(1):7028. doi: 10.1038/s41467-023-42732-2.

DOI:10.1038/s41467-023-42732-2
PMID:37919280
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10622560/
Abstract

The leishmanin skin test was used for almost a century to detect exposure and immunity to Leishmania, the causative agent of leishmaniasis, a major neglected tropical disease. Due to a lack of antigen used for the intradermal injection, the leishmanin skin test is no longer available. As leishmaniasis control programs are advancing and new vaccines are entering clinical trials, it is essential to re-introduce the leishmanin skin test. Here we establish a Leishmania donovani strain and describe the production, under Good Laboratory Practice conditions, of leishmanin soluble antigen used to induce the leishmanin skin test in animal models of infection and vaccination. Using a mouse model of cutaneous leishmaniasis and a hamster model of visceral leishmaniasis, soluble antigen induces a leishmanin skin test response following infection and vaccination with live attenuated Leishmania major (LmCen). Both the CD4 and CD8 T-cells are necessary for the leishmanin skin test response. This study demonstrates the feasibility of large-scale production of leishmanin antigen addressing a major bottleneck for performing the leishmanin skin test in future surveillance and vaccine clinical trials.

摘要

利什曼素皮肤试验曾用于近一个世纪，以检测利什曼原虫（导致利什曼病的病原体）的暴露和免疫情况，而利什曼病是一种主要的被忽视热带病。由于皮内注射所用抗原的缺乏，利什曼素皮肤试验已不再可用。随着利什曼病控制项目的推进和新疫苗进入临床试验，重新引入利什曼素皮肤试验至关重要。在这里，我们建立了一株杜氏利什曼原虫，并描述了在良好实验室规范条件下生产利什曼素可溶性抗原，用于在感染和接种减毒活利什曼原虫（LmCen）的动物模型中诱导利什曼素皮肤试验。使用皮肤利什曼病的小鼠模型和内脏利什曼病的仓鼠模型，可溶性抗原在感染和接种后诱导利什曼素皮肤试验反应。CD4 和 CD8 T 细胞均对利什曼素皮肤试验反应必不可少。本研究证明了大规模生产利什曼素抗原的可行性，解决了未来监测和疫苗临床试验中进行利什曼素皮肤试验的主要瓶颈。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b29c/10622560/84c86d27648b/41467_2023_42732_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b29c/10622560/2da38732156c/41467_2023_42732_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b29c/10622560/45581c77bdec/41467_2023_42732_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b29c/10622560/9615dc829538/41467_2023_42732_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b29c/10622560/d8e9c56a54db/41467_2023_42732_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b29c/10622560/5989f366b7de/41467_2023_42732_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b29c/10622560/84c86d27648b/41467_2023_42732_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b29c/10622560/2da38732156c/41467_2023_42732_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b29c/10622560/45581c77bdec/41467_2023_42732_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b29c/10622560/9615dc829538/41467_2023_42732_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b29c/10622560/d8e9c56a54db/41467_2023_42732_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b29c/10622560/5989f366b7de/41467_2023_42732_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b29c/10622560/84c86d27648b/41467_2023_42732_Fig6_HTML.jpg

相似文献

[1]
Production of leishmanin skin test antigen from Leishmania donovani for future reintroduction in the field.

Nat Commun. 2023-11-2

[2]
A review of the leishmanin skin test: A neglected test for a neglected disease.

PLoS Negl Trop Dis. 2021-7

[3]
Revival of Leishmanization and Leishmanin.

Front Cell Infect Microbiol. 2021-3-17

[4]
Leishmanin and tuberculin sensitivity in leishmaniasis in the Sudan, with special reference to kala-azar.

Trans R Soc Trop Med Hyg. 1993

[5]
Characterization of human T lymphocyte-mediated immune responses induced by a vaccine against American tegumentary leishmaniasis.

Am J Trop Med Hyg. 1995-8

[6]
Immune responses induced by the Leishmania (Leishmania) donovani A2 antigen, but not by the LACK antigen, are protective against experimental Leishmania (Leishmania) amazonensis infection.

Infect Immun. 2003-7

[7]
In vivo evaluation of immune responses in leishmaniasis: the use of cross-species leishmanin preparations for skin testing.

Am J Trop Med Hyg. 1995-7

[8]
Leishmania donovani p36(LACK) DNA vaccine is highly immunogenic but not protective against experimental visceral leishmaniasis.

Infect Immun. 2001-8

[9]
[Eco-epidemiology of visceral and cutaneous leishmaniasis in the Arab Republic of Yemen. II. A survey using intradermal reaction to leishmanin in a zone of mixed infestation with Leishmania tropica, L. donovani and L. infantum].

Bull Soc Pathol Exot Filiales. 1989

[10]
Dichotomy of protective cellular immune responses to human visceral leishmaniasis.

Clin Exp Immunol. 2005-5

引用本文的文献

[1]
Design and development of highly conserved, HLA-promiscuous T cell multiepitope vaccines against human visceral leishmaniasis.

Front Immunol. 2025-3-31

[2]
Atypical cutaneous leishmaniasis: a new challenge to VL elimination in South-East Asia.

Front Cell Infect Microbiol. 2024

[3]
Demographic characteristics and prevalence of asymptomatic infection in migrant workers working in an endemic area in Northwest Ethiopia.

Front Epidemiol. 2024-4-9

[4]
The Preclinical Validation of 405 nm Light Parasiticidal Efficacy on in Ex Vivo Platelets in a Rag2 Mouse Model.

Microorganisms. 2024-1-29

本文引用的文献

[1]
Leishmania donovani hybridisation and introgression in nature: a comparative genomic investigation.

Lancet Microbe. 2021-6

[2]
From infection to vaccination: reviewing the global burden, history of vaccine development, and recurring challenges in global leishmaniasis protection.

Expert Rev Vaccines. 2021-11

[3]
Preclinical validation of a live attenuated dermotropic Leishmania vaccine against vector transmitted fatal visceral leishmaniasis.

Commun Biol. 2021-7-30

[4]
A review of the leishmanin skin test: A neglected test for a neglected disease.

PLoS Negl Trop Dis. 2021-7

[5]
Understanding the immune responses involved in mediating protection or immunopathology during leishmaniasis.

Biochem Soc Trans. 2021-2-26

[6]
Characterization of a new Leishmania major strain for use in a controlled human infection model.

Nat Commun. 2021-1-11

[7]
A second generation leishmanization vaccine with a markerless attenuated Leishmania major strain using CRISPR gene editing.

Nat Commun. 2020-7-10

[8]
Impact of the visceral leishmaniasis elimination initiative on Leishmania donovani transmission in Nepal: a 10-year repeat survey.

Lancet Glob Health. 2020-2

[9]
Eliminating visceral leishmaniasis in South Asia: the road ahead.

BMJ. 2019-1-22

[10]
Age trends in asymptomatic and symptomatic Leishmania donovani infection in the Indian subcontinent: A review and analysis of data from diagnostic and epidemiological studies.

PLoS Negl Trop Dis. 2018-12-6

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