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DAR-901加强疫苗在小鼠结核病模型中的免疫原性和保护效力

Immunogenicity and Protective Efficacy of the DAR-901 Booster Vaccine in a Murine Model of Tuberculosis.

作者信息

Lahey Timothy, Laddy Dominick, Hill Krystal, Schaeffer Jacqueline, Hogg Alison, Keeble James, Dagg Belinda, Ho Mei Mei, Arbeit Robert D, von Reyn C Fordham

机构信息

Dartmouth's Geisel School of Medicine, 1 Medical Center Drive, Lebanon, NH, United States of America.

Aeras, 1405 Research Blvd. Rockville, MD United States of America.

出版信息

PLoS One. 2016 Dec 20;11(12):e0168521. doi: 10.1371/journal.pone.0168521. eCollection 2016.

DOI:10.1371/journal.pone.0168521
PMID:27997597
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5173179/
Abstract

BACKGROUND

The development of a novel tuberculosis vaccine is a leading global health priority. SRL172, an inactivated, whole-cell mycobacterial vaccine, was safe, immunogenic and reduced the incidence of culture-confirmed tuberculosis in a phase III trial in HIV-infected and BCG immunized adults in Tanzania. Here we describe the immunogenicity and protective efficacy of DAR-901, a booster vaccine against tuberculosis manufactured from the same seed strain using a new scalable method.

METHODS

We evaluated IFN-γ responses by ELISpot and antibody responses by enzyme linked immunosorbent assay in C57BL/6 and BALB/c mice after three doses of DAR-901. In an aerosol challenge model, we evaluated the protective efficacy of the DAR-901 booster in C57BL/6 mice primed with BCG and boosted with two doses of DAR-901 at 4 dosage levels in comparison with homologous BCG boost.

RESULTS

DAR-901 vaccination elicited IFN-γ responses to mycobacterial antigen preparations derived from both DAR-901 and Mycobacterium tuberculosis. DAR-901 immunization enhanced antibody responses to DAR-901 but not Mycobacterium tuberculosis lysate or purified protein derivative. Among animals primed with BCG, boosting with DAR-901 at 1 mg provided greater protection against aerosol challenge than a homologous BCG boost (lungs P = 0.036, spleen P = 0.028).

CONCLUSIONS

DAR-901 induces cellular and humoral immunity and boosts protection from M. tuberculosis compared to a homologous BCG boost.

摘要

背景

开发新型结核病疫苗是全球主要的卫生优先事项。SRL172是一种灭活的全细胞分枝杆菌疫苗，在坦桑尼亚对感染HIV且接种过卡介苗的成年人进行的III期试验中，该疫苗安全、具有免疫原性并降低了培养确诊结核病的发病率。在此，我们描述了DAR - 901的免疫原性和保护效力，DAR - 901是一种使用新的可扩展方法由同一种子菌株生产的结核病加强疫苗。

方法

在给C57BL/6和BALB/c小鼠接种三剂DAR - 901后，我们通过酶联免疫斑点法评估了γ干扰素反应，并通过酶联免疫吸附测定法评估了抗体反应。在气溶胶攻击模型中，我们评估了DAR - 901加强疫苗在接种卡介苗并以4个剂量水平接种两剂DAR - 901进行加强的C57BL/6小鼠中的保护效力，并与同源卡介苗加强进行了比较。

结果

接种DAR - 901引发了对源自DAR - 901和结核分枝杆菌的分枝杆菌抗原制剂的γ干扰素反应。DAR - 901免疫增强了对DAR - 901的抗体反应，但对结核分枝杆菌裂解物或纯化蛋白衍生物没有增强作用。在接种卡介苗的动物中，用1mg的DAR - 901进行加强比同源卡介苗加强对气溶胶攻击提供了更好的保护（肺部P = 0.036，脾脏P = 0.028）。

结论

与同源卡介苗加强相比，DAR - 901可诱导细胞免疫和体液免疫，并增强对结核分枝杆菌的保护作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/367d/5173179/8a4aff7c3f8f/pone.0168521.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/367d/5173179/59f8f75c14af/pone.0168521.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/367d/5173179/ef01b95d4164/pone.0168521.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/367d/5173179/72af0f58a629/pone.0168521.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/367d/5173179/8a4aff7c3f8f/pone.0168521.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/367d/5173179/59f8f75c14af/pone.0168521.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/367d/5173179/ef01b95d4164/pone.0168521.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/367d/5173179/72af0f58a629/pone.0168521.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/367d/5173179/8a4aff7c3f8f/pone.0168521.g004.jpg

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