Young Andrew, Kolekar Sharada, Mendoza Carlos Alvarez, Jaberolansar Noushin, Modhiran Naphak, Webb Tim, McCuaig Robert, Kommajosyula Varsha, Tardiota Nicolas, Dy Quimbe, Amarilla Alberto A, Dalrymple Rhiannon L, Gillard Marianne, Dutton Julie L, Magdalena Juana, Vandendriessche Frank, Smal Jean, Young Paul R, Watterson Daniel, Hanon Emmanuel J, Chappell Keith J
The Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St Lucia, Queensland, Australia.
School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, Queensland, Australia.
PLoS Pathog. 2025 Jul 17;21(7):e1013312. doi: 10.1371/journal.ppat.1013312. eCollection 2025 Jul.
Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) are two medically important causes of respiratory tract infections and diseases. After more than five decades of research and development, vaccines have recently been approved for the prevention of lower respiratory tract disease caused by RSV. However, vaccines for hMPV remain in early-stage development. Here we describe the design and characterisation as well as pre-clinical development of a bivalent vaccine, VXB-241, comprised of the recombinantly expressed viral fusion proteins from both RSV and hMPV, stabilised in their pre-fusion conformation by combining the use of two technologies, the second-generation molecular clamp (MC2S) and key pre-fusion stabilizing mutations. Each of the two antigens were produced at high yield in a mammalian expression system and purified by an affinity capture resin specific to MC2S. Each antigen was demonstrated to adopt the pre-fusion conformation, which was stable for at least twelve months in liquid formulation at 2-8°C. Head-to-head evaluation in mouse immunogenicity studies showed that the VXB-241 candidate vaccine induced a neutralising immune response that was superior or equivalent to the pre-fusion stabilised comparator antigens for either RSV or hMPV, including the RSVPreF3 antigen of the licensed RSV vaccine, Arexvy (GSK). The results presented here have supported progression of VXB-241 into a Phase 1 clinical trial which commenced enrolment in August 2024 (ClinicalTrials.gov ID NCT06556147).
呼吸道合胞病毒（RSV）和人偏肺病毒（hMPV）是引起呼吸道感染和疾病的两个重要医学病因。经过五十多年的研发，近期已批准了用于预防RSV所致下呼吸道疾病的疫苗。然而，针对hMPV的疫苗仍处于早期研发阶段。在此，我们描述了一种二价疫苗VXB - 241的设计、特性以及临床前开发情况，该疫苗由RSV和hMPV的重组表达病毒融合蛋白组成，通过结合使用第二代分子钳（MC2S）和关键的融合前稳定突变这两种技术，使其稳定在融合前构象。两种抗原均在哺乳动物表达系统中高产表达，并通过特异性针对MC2S的亲和捕获树脂进行纯化。每种抗原均被证明采用融合前构象，在2 - 8°C的液体制剂中至少十二个月保持稳定。在小鼠免疫原性研究中的直接比较评估表明，VXB - 241候选疫苗诱导的中和免疫反应优于或等同于针对RSV或hMPV的融合前稳定对照抗原，包括已获许可的RSV疫苗Arexvy（葛兰素史克公司）的RSVPreF3抗原。此处呈现的结果支持VXB - 241进入1期临床试验，该试验于2024年8月开始招募受试者（ClinicalTrials.gov标识符NCT06556147）。
