Cates Zoë Parker, Facciuolo Antonio, Scruten Erin, Kusalik Anthony, Napper Scott
Department of Computer Science, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
Vaccine and Infectious Disease Organization (VIDO), University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
PLoS One. 2025 Sep 4;20(9):e0330741. doi: 10.1371/journal.pone.0330741. eCollection 2025.
Vaccines of enhanced range of protection could help to control newly emerging infectious diseases while providing greater resilience to any subsequent variants. Such "universal vaccines" are an idealized, but unrealized, goal that may benefit from unbiased, high-throughput approaches that define antibody cross-reactivity to enable rational selection of cross-protective epitopes. The priority of this investigation is to establish a pipeline for the identification and preliminary characterization of epitopes with enhanced cross-reactivity. A peptide immunoarray representing the proteomes of SARS-CoV, SARS-CoV-II, and MERS-CoV was applied to characterize spike glycoprotein-specific antibody populations within convalescence serum of SARS-CoV-II infected ferrets. Through two alternate bioinformatic approaches, twenty candidate epitopes were identified and translated into vaccines. Epitopes inducing antibodies with cross-reactivity across naturally occurring versions of spike glycoprotein, including SARS-CoV-II Delta and Omicron variants, as well as antigenically distant SARS-CoV and MERS-CoV, were identified. Working from the assumption that cross-reactivity is prerequisite for cross-protection, this highlights the opportunity and mechanisms by which immunoarrays, coupled with in vitro screening assays, can enable rational selection of epitopes with enhanced potential for cross-protection.
具有更广泛保护范围的疫苗有助于控制新出现的传染病，同时增强对任何后续变体的抵抗力。这种“通用疫苗”是一个理想化但尚未实现的目标，可能受益于无偏见的高通量方法，这些方法可定义抗体交叉反应性，从而合理选择交叉保护表位。本研究的重点是建立一个用于鉴定和初步表征具有增强交叉反应性表位的流程。应用代表SARS-CoV、SARS-CoV-II和MERS-CoV蛋白质组的肽免疫阵列来表征SARS-CoV-II感染雪貂恢复期血清中的刺突糖蛋白特异性抗体群体。通过两种交替的生物信息学方法，鉴定了20个候选表位并将其转化为疫苗。鉴定出了能诱导产生对天然存在的刺突糖蛋白版本具有交叉反应性抗体的表位，包括SARS-CoV-II Delta和Omicron变体，以及抗原性较远的SARS-CoV和MERS-CoV。基于交叉反应性是交叉保护的先决条件这一假设，这凸显了免疫阵列与体外筛选试验相结合能够合理选择具有增强交叉保护潜力表位的机会和机制。
