Department of Medicine, British Columbia Centre for Disease Control, University of British Columbia, Vancouver, BC, Canada.
Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, United States.
Front Cell Infect Microbiol. 2024 Feb 2;14:1342621. doi: 10.3389/fcimb.2024.1342621. eCollection 2024.
Murine research has revealed a significant role for antibody responses in protection against reinfection. To explore potential humoral immune markers of protection elicited by (CT) antigens in humans in the context of presumed clinical correlates of protection, we used both an IgG1-based ELISA and a conventional total IgG ELISA to evaluate antibody responses. We evaluated responses to five CT outer membrane proteins (PmpE, PmpF, PmpG, PmpH, and MOMP), along with other promising CT antigens (Pgp3 and HSP60), negative control antigens (RecO and AtpE), and CT elementary bodies (EBs) in sera from a well-characterized cohort of 60 women with different CT infection outcomes, including two outcomes that are likely clinical correlates of protective immunity: spontaneous resolution of infection and absence of reinfection after treatment. Furthermore, we used a flow cytometry-based assay to measure antibody-mediated phagocytosis by neutrophils in these sera. Results demonstrated that IgG1 ELISA displayed higher sensitivity than conventional total IgG ELISA in assessing antibody responses to CT EBs and antigens. Pgp3 IgG1 ELISA exhibited the highest sensitivity compared to IgG1 ELISA incorporating CT EBs or other antigens, confirming Pgp3 IgG1 ELISA as an ideal assay for CT antibody detection. Most (95%) sera from women with CT infection outcomes exhibited antibody-mediated phagocytosis of CT EBs, which was significantly correlated with IgG1 antibody responses to MOMP, Pgp3, HSP60, and PmpF. However, neither IgG1 responses to CT antigens and EBs nor antibody-mediated phagocytosis were associated with clinical correlates of protection. These findings suggest that neither CT IgG1 antibody detection nor antibody-mediated phagocytosis will be useful as immune correlates of protection against CT infection in humans.
鼠类研究揭示了抗体反应在预防再感染中的重要作用。为了在假定的保护临床相关因素的背景下,探索人类对(CT)抗原产生的潜在体液免疫保护标记物,我们使用 IgG1 为基础的 ELISA 和传统的总 IgG ELISA 来评估抗体反应。我们评估了对五种 CT 外膜蛋白(PmpE、PmpF、PmpG、PmpH 和 MOMP)以及其他有前途的 CT 抗原(Pgp3 和 HSP60)、阴性对照抗原(RecO 和 AtpE)和 CT 元体(EBs)的反应,这些反应来自于一个具有不同 CT 感染结果的 60 名女性的特征良好的队列,包括两个可能是保护性免疫的临床相关因素:感染的自发消退和治疗后无再感染。此外,我们使用基于流式细胞术的测定法来测量这些血清中抗体介导的中性粒细胞吞噬作用。结果表明,IgG1 ELISA 在评估 CT EBs 和抗原的抗体反应方面比传统的总 IgG ELISA 具有更高的灵敏度。与包含 CT EBs 或其他抗原的 IgG1 ELISA 相比,Pgp3 IgG1 ELISA 显示出最高的灵敏度,证实 Pgp3 IgG1 ELISA 是 CT 抗体检测的理想测定法。大多数(95%)来自 CT 感染结果的女性的血清显示出对 CT EBs 的抗体介导的吞噬作用,这与 MOMP、Pgp3、HSP60 和 PmpF 的 IgG1 抗体反应显著相关。然而,无论是 CT 抗原和 EBs 的 IgG1 反应,还是抗体介导的吞噬作用,都与保护临床相关因素无关。这些发现表明,CT IgG1 抗体检测或抗体介导的吞噬作用都不会作为人类对抗 CT 感染的保护免疫相关因素有用。
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