Table_1_Determining Immune and miRNA Biomarkers Related to Respiratory Syncytial Virus (RSV) Vaccine Types.docx

Respiratory Syncytial Virus (RSV) causes serious respiratory tract illness and substantial morbidity and some mortality in populations at the extremes of age, i.e., infants, young children, and the elderly. To date, RSV vaccine development has been unsuccessful, a feature linked to the lack of biomarkers available to assess the safety and efficacy of RSV vaccine candidates. We examined microRNAs (miR) as potential biomarkers for different types of RSV vaccine candidates. In this study, mice were vaccinated with a live attenuated RSV candidate that lacks the small hydrophobic (SH) and attachment (G) proteins (CP52), an RSV G protein microparticle (GA2-MP) vaccine, a formalin-inactivated RSV (FI-RSV) vaccine or were mock-treated. Several immunological endpoints and miR expression profiles were determined in mouse serum and bronchoalveolar lavage (BAL) following vaccine priming, boost, and RSV challenge. We identified miRs that were linked with immunological parameters of disease and protection. We show that miRs are potential biomarkers providing valuable insights for vaccine development.

呼吸道合胞病毒（RSV）可引起严重的呼吸道疾病，并在年龄极端人群中，即婴儿、幼儿和老年人群中，导致显著的发病率以及部分死亡率。迄今为止，RSV 疫苗的研发尚未取得成功，这一特点与评估 RSV 疫苗候选物安全性和有效性的生物标志物缺乏有关。本研究中，我们探讨了微RNA（miR）作为不同类型 RSV 疫苗候选物的潜在生物标志物。在本研究中，小鼠被接种了缺乏小疏水性（SH）和结合（G）蛋白（CP52）的减毒活 RSV 候选疫苗、RSV G 蛋白微粒子（GA2-MP）疫苗、甲醛灭活 RSV（FI-RSV）疫苗，或接受了模拟治疗。在疫苗初免、加强免疫和 RSV 挑战后，测定了小鼠血清和支气管肺泡灌洗液（BAL）中的多个免疫学终点和 miR 表达谱。我们确定了与疾病免疫学参数和保护相关的 miR。我们表明，miR 作为潜在的生物标志物，为疫苗研发提供了宝贵的见解。