Shigella-Specific Immune Profiles Induced after Parenteral Immunization or Oral Challenge with Either Shigella flexneri 2a or Shigella sonnei.
Shigella-Specific Immune Profiles Induced after Parenteral Immunization or Oral Challenge with Either Shigella flexneri 2a or Shigella sonnei.
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DOI：
10.1128/msphere.00122-21
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发表时间：
2021-08-25
期刊：
影响因子：
4.8
通讯作者：
Kaminski RW
中科院分区：
文献类型：
--
作者：
Clarkson KA;Porter CK;Talaat KR;Frenck RW Jr;Alaimo C;Martin P;Bourgeois AL;Kaminski RW
志贺氏菌属是全球腹泻相关发病率和死亡率的主要原因。开发和广泛实施有效的疫苗仍然是降低志贺氏菌特异性发病率的最佳选择。不幸的是，缺乏明确的志贺氏菌保护相关性继续阻碍疫苗的开发工作。志贺氏菌控制的人类感染模型（CHIM）通常用于疫苗开发的早期阶段，以提供疫苗功效的初步估计；然而，CHIM 还提供了在疫苗接种前后或感染前后进行深入免疫反应特征分析的机会。在本研究中，使用主成分分析来检查最近两种志贺氏菌 CHIM 的免疫反应数据，以表征与肠胃外免疫、福氏志贺氏菌 2a 口服攻击或宋内志贺氏菌口服攻击相关的免疫反应特征。尽管肠胃外免疫诱导了以强烈的全身抗体反应为特征的免疫特征，但它也包括粘膜反应。有趣的是，与 S. sonnei 相比，福氏链球菌 2a 的口服攻击引起了明显不同的情况，其特征是相对平衡的全身和粘膜反应。相比之下，宋内沙门氏菌诱导粘膜抗体大幅增加，而攻击后志贺氏菌病结果的全身反应没有差异。此外，与 S. sonnei 相比，福氏链球菌 2a 攻击诱导的肠道炎症水平显着更高，这表明两种血清型在触发先天免疫的诱导和激活方式方面也可能有所不同。这些发现可能对志贺氏菌疫苗的开发具有重要意义，因为不同志贺氏菌血清型的保护性免疫机制可能有所不同。重要性 尽管志贺氏菌病的免疫保护相关性尚未确定，但先前的研究已证明志贺氏菌感染以血清型特异性方式提供针对再次感染的保护。因此，口服攻击后患有中度至重度疾病的受试者可能会受到保护，免受同源再攻击，并且研究这些受试者的免疫反应可能有助于识别与保护性免疫发展相关的免疫标志物。这是第一项描述两种不同志贺氏菌血清型口服攻击后不同的先天性和适应性免疫特征的研究。这里进行的分析为根据志贺氏菌血清型引发保护性免疫所需的不同免疫机制的潜力提供了重要的见解。这种差异可能会对志贺氏菌领域内的疫苗设计和开发产生重大影响，应针对多种志贺氏菌血清型进行进一步研究。
Shigella spp. are a leading cause of diarrhea-associated global morbidity and mortality. Development and widespread implementation of an efficacious vaccine remain the best option to reduce Shigella-specific morbidity. Unfortunately, the lack of a well-defined correlate of protection for shigellosis continues to hinder vaccine development efforts. Shigella controlled human infection models (CHIM) are often used in the early stages of vaccine development to provide preliminary estimates of vaccine efficacy; however, CHIMs also provide the opportunity to conduct in-depth immune response characterizations pre- and postvaccination or pre- and postinfection. In the current study, principal-component analyses were used to examine immune response data from two recent Shigella CHIMs in order to characterize immune response profiles associated with parenteral immunization, oral challenge with Shigella flexneri 2a, or oral challenge with Shigella sonnei. Although parenteral immunization induced an immune profile characterized by robust systemic antibody responses, it also included mucosal responses. Interestingly, oral challenge with S. flexneri 2a induced a distinctively different profile compared to S. sonnei, characterized by a relatively balanced systemic and mucosal response. In contrast, S. sonnei induced robust increases in mucosal antibodies with no differences in systemic responses across shigellosis outcomes postchallenge. Furthermore, S. flexneri 2a challenge induced significantly higher levels of intestinal inflammation compared to S. sonnei, suggesting that both serotypes may also differ in how they trigger induction and activation of innate immunity. These findings could have important implications for Shigella vaccine development as protective immune mechanisms may differ across Shigella serotypes. IMPORTANCE Although immune correlates of protection have yet to be defined for shigellosis, prior studies have demonstrated that Shigella infection provides protection against reinfection in a serotype-specific manner. Therefore, it is likely that subjects with moderate to severe disease post-oral challenge would be protected from a homologous rechallenge, and investigating immune responses in these subjects may help identify immune markers associated with the development of protective immunity. This is the first study to describe distinct innate and adaptive immune profiles post-oral challenge with two different Shigella serotypes. Analyses conducted here provide essential insights into the potential of different immune mechanisms required to elicit protective immunity, depending on the Shigella serotype. Such differences could have significant impacts on vaccine design and development within the Shigella field and should be further investigated across multiple Shigella serotypes.
影响因子：
3.7
作者：
Davis CL;Wahid R;Toapanta FR;Simon JK;Sztein MB;Levy D
通讯作者：
Levy D