Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA.
Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA; Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX, USA; Department of Pharmacology and Chemical Biology, Baylor College of Medicine, Houston, TX, USA.
Vaccine. 2022 Jan 24;40(3):536-543. doi: 10.1016/j.vaccine.2021.11.087. Epub 2021 Dec 10.
The respiratory syncytial virus (RSV) fusion (F) protein undergoes two furin-cleavage events to become fusion competent, resulting in the release of a twenty-seven amino acid peptide (p27). Recent studies indicate that the p27 region of the F protein was an immunodominant antigen in young children. In this study, we evaluated the kinetics of the serum antibody response to the p27 peptide following natural RSV reinfection in adults. Nineteen healthy adults under sixty-five years of age were enrolled during the 2018-2019 RSV season in Houston, TX. Blood was collected at three study visits and RSV infection status was defined by changes in neutralizing antibody resulting in three groups: uninfected (n = 12), acutely infected (n = 4), and recently infected (n = 3). Serum IgG and IgA antibodies against RSV/A and RSV/B p27 peptides were measured by enzyme-linked immunosorbent assays, and serum p27-like antibodies were detected by a p27 competitive antibody assay. Anti-p27 antibodies were detected in all subjects at each study visit. The measured IgG and IgA anti-p27 antibody levels followed the same pattern as other RSV site-specific and neutralizing antibody responses described for this cohort previously: the uninfected group had stable responses for the duration of the study period, the acutely infected group had a significant increase following RSV infection, and the recently infected group had a decrease in anti-p27 antibody during the study period. These results indicate that antibodies to the p27 region of the F protein are generated following natural RSV reinfection and suggest that some of the F protein is potentially in a partially cleaved state on the surface of virions, expanding on the previous assumption that all of p27 is post-translationally released and not present on mature F. Additionally, antibody responses were significantly lower (1.4-1.5-fold) toward RSV/B than to RSV/A p27 at each study visit, despite being an RSV/B dominant outbreak. Understanding the mechanism for the differences in the magnitude of the RSV/A and RSV/B p27 antibody response may enhance our understanding of the intracellular processing of the F protein.
呼吸道合胞病毒 (RSV) 融合 (F) 蛋白经历两次弗林裂解事件才能成为融合有效，导致释放 27 个氨基酸肽 (p27)。最近的研究表明，F 蛋白的 p27 区域是幼儿中的免疫优势抗原。在这项研究中，我们评估了成年人在自然 RSV 再感染后对 p27 肽的血清抗体反应的动力学。在德克萨斯州休斯顿的 2018-2019 RSV 季节期间，招募了 19 名 65 岁以下的健康成年人。在三个研究访视时采集血液，通过中和抗体的变化定义 RSV 感染状态，将其分为三组：未感染 (n=12)、急性感染 (n=4) 和近期感染 (n=3)。通过酶联免疫吸附试验测量针对 RSV/A 和 RSV/B p27 肽的血清 IgG 和 IgA 抗体，并通过 p27 竞争抗体测定检测血清 p27 样抗体。在每个研究访视时，所有受试者均检测到抗-p27 抗体。测量的 IgG 和 IgA 抗-p27 抗体水平与之前为该队列描述的其他 RSV 特异性和中和抗体反应遵循相同的模式：未感染组在整个研究期间保持稳定的反应，急性感染组在 RSV 感染后显著增加，而近期感染组在研究期间抗-p27 抗体减少。这些结果表明，在自然 RSV 再感染后会产生针对 F 蛋白 p27 区域的抗体，并表明病毒表面的 F 蛋白的一部分处于部分裂解状态，扩展了之前的假设，即所有 p27 都是翻译后释放的，而不是存在于成熟 F 上。此外，尽管 RSV/B 是优势爆发，但在每个研究访视时，针对 RSV/B 的抗体反应显著低于针对 RSV/A 的 p27 (1.4-1.5 倍)。了解 RSV/A 和 RSV/B p27 抗体反应幅度差异的机制可能会增强我们对 F 蛋白细胞内加工的理解。
