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保守分子伴侣蛋白PrsA刺激针对A组链球菌的保护性免疫。

Conserved molecular chaperone PrsA stimulates protective immunity against group A Streptococcus.

作者信息

Lai Chien-Yu, Xie Jia-Xun, Lai Meng-Chih, Wu Zhao-Yi, Lin Jr-Shiuan, Huang Yu-Tsung, Chi Chia-Yu, Chiang-Ni Chuan, Walker Mark J, Chang Yung-Chi

机构信息

Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei, 10051, Taiwan.

Graduate Institute of Immunology, College of Medicine, National Taiwan University, Taipei, 10051, Taiwan.

出版信息

NPJ Vaccines. 2024 Feb 26;9(1):46. doi: 10.1038/s41541-024-00839-7.

DOI:10.1038/s41541-024-00839-7
PMID:38409165
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10897429/
Abstract

Group A Streptococcus (GAS) is a significant human pathogen that poses a global health concern. However, the development of a GAS vaccine has been challenging due to the multitude of diverse M-types and the risk of triggering cross-reactive immune responses. Our previous research has identified a critical role of PrsA1 and PrsA2, surface post-translational molecular chaperone proteins, in maintaining GAS proteome homeostasis and virulence traits. In this study, we aimed to further explore the potential of PrsA1 and PrsA2 as vaccine candidates for preventing GAS infection. We found that PrsA1 and PrsA2 are highly conserved among GAS isolates, demonstrating minimal amino acid variation. Antibodies specifically targeting PrsA1/A2 showed no cross-reactivity with human heart proteins and effectively enhanced neutrophil opsonophagocytic killing of various GAS serotypes. Additionally, passive transfer of PrsA1/A2-specific antibodies conferred protective immunity in infected mice. Compared to alum, immunization with CFA-adjuvanted PrsA1/A2 induced higher levels of Th1-associated IgG isotypes and complement activation and provided approximately 70% protection against invasive GAS challenge. These findings highlight the potential of PrsA1 and PrsA2 as universal vaccine candidates for the development of an effective GAS vaccine.

摘要

A组链球菌（GAS）是一种重要的人类病原体，引起全球健康关注。然而，由于多种不同的M型以及引发交叉反应性免疫反应的风险，GAS疫苗的研发一直具有挑战性。我们之前的研究已经确定，表面翻译后分子伴侣蛋白PrsA1和PrsA2在维持GAS蛋白质组稳态和毒力特性方面起着关键作用。在本研究中，我们旨在进一步探索PrsA1和PrsA2作为预防GAS感染候选疫苗的潜力。我们发现，PrsA1和PrsA2在GAS分离株中高度保守，氨基酸变异极小。特异性靶向PrsA1/A2的抗体与人心脏蛋白无交叉反应，并有效增强了中性粒细胞对各种GAS血清型的调理吞噬杀伤作用。此外，PrsA1/A2特异性抗体的被动转移在感染小鼠中赋予了保护性免疫。与明矾相比，用CFA佐剂的PrsA1/A2免疫诱导了更高水平的Th1相关IgG同种型和补体激活，并提供了约70%的针对侵袭性GAS攻击的保护。这些发现突出了PrsA1和PrsA2作为开发有效GAS疫苗的通用候选疫苗的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/11c0/10897429/85a09a0d895f/41541_2024_839_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/11c0/10897429/353e23035053/41541_2024_839_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/11c0/10897429/89a48c049263/41541_2024_839_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/11c0/10897429/c7604d4b9267/41541_2024_839_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/11c0/10897429/1182413b6012/41541_2024_839_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/11c0/10897429/85a09a0d895f/41541_2024_839_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/11c0/10897429/353e23035053/41541_2024_839_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/11c0/10897429/89a48c049263/41541_2024_839_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/11c0/10897429/c7604d4b9267/41541_2024_839_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/11c0/10897429/1182413b6012/41541_2024_839_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/11c0/10897429/85a09a0d895f/41541_2024_839_Fig5_HTML.jpg

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Nat Commun. 2023 Sep 25;14(1):5963. doi: 10.1038/s41467-023-41410-7.
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Flanking N- and C-terminal domains of PrsA in type 2 are crucial for inducing cell death independent of TLR2 recognition.2 型 PrsA N 端和 C 端侧翼结构域对 TLR2 识别无依赖性的细胞死亡诱导至关重要。
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Polymeric epitope-based vaccine induces protective immunity against group A Streptococcus.
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NPJ Vaccines. 2023 Jul 14;8(1):102. doi: 10.1038/s41541-023-00695-x.
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Modeling the potential health impact of prospective Strep A vaccines.模拟A群链球菌前瞻性疫苗的潜在健康影响。
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