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与卡介苗接种相比,MTBVAC在非人灵长类动物中诱导产生更高的抗体滴度和IgG亲和力。

MTBVAC induces superior antibody titers and IgG avidity compared to BCG vaccination in non-human primates.

作者信息

Peralta-Álvarez Marco Polo, Downward Keya, White Andrew, Redondo Azema Hugo, Sibley Laura, Sarfas Charlotte, Morrison Alexandra, Dennis Mike, Diaz-Santana Delia, Harris Stephanie A, Li Shuailin, Puentes Eugenia, Aguilo Nacho, Martin Carlos, Sharpe Sally, McShane Helen, Tanner Rachel

机构信息

Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.

Laboratorio Nacional de Vacunologia y Virus Tropicales, Departamento de Microbiologia, Escuela Nacional de Ciencias Biologicas, Instituto Politecnico Nacional, Ciudad de Mexico, Mexico.

出版信息

NPJ Vaccines. 2024 Nov 20;9(1):230. doi: 10.1038/s41541-024-01009-5.

Abstract

The only currently licensed vaccine against tuberculosis (TB), Bacille Calmette Guérin (BCG), is insufficient to control the epidemic. MTBVAC is a live attenuated strain of Mycobacterium tuberculosis (M.tb) and is one the most advanced TB vaccine candidates in the pipeline. It is more efficacious than BCG in preclinical models including non-human primates (NHPs), and has demonstrated safety and immunogenicity in human populations. To better understand the immune mechanisms underlying the superior efficacy conferred by MTBVAC, we characterized M.tb-specific antibody responses in NHPs vaccinated with either BCG or MTBVAC. MTBVAC vaccination induced higher titers of IgG, IgM and IgA, and higher avidity IgG compared with BCG vaccination. IgG avidity correlated with protection following M.tb challenge in the same animals, validating the association previously reported between this measure and protection in the context of intravenous BCG vaccination, suggesting that IgG avidity may represent a relevant marker or correlate of protection from TB.

摘要

目前唯一获得许可的抗结核病疫苗卡介苗(BCG),不足以控制结核病的流行。MTBVAC是一种减毒活结核分枝杆菌菌株,是正在研发的最先进的结核病疫苗候选物之一。在包括非人灵长类动物(NHP)在内的临床前模型中,它比卡介苗更有效,并且已在人群中证明了安全性和免疫原性。为了更好地理解MTBVAC所赋予的卓越疗效背后的免疫机制,我们对接种卡介苗或MTBVAC的非人灵长类动物体内的结核分枝杆菌特异性抗体反应进行了表征。与接种卡介苗相比,接种MTBVAC诱导产生了更高滴度的IgG、IgM和IgA,以及更高亲和力的IgG。在同一批动物中,IgG亲和力与结核分枝杆菌攻击后的保护作用相关,证实了先前报道的在静脉注射卡介苗情况下该指标与保护作用之间的关联,这表明IgG亲和力可能是预防结核病的一个相关标志物或保护作用的相关指标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e652/11579480/8900b264421f/41541_2024_1009_Fig1_HTML.jpg

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