Meyer Michelle, Gunn Bronwyn M, Pietzsch Colette, Subramani Chandru, Kedarinath Kritika, Villarreal Paula P, Hyde Matthew A, Saphire Erica Ollmann, Crowe James E, Alter Galit, Himansu Sunny, Carfi Andrea, Bukreyev Alexander
Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA.
Galveston National Laboratory, Galveston, TX, USA.
Nat Commun. 2025 Jul 1;16(1):5702. doi: 10.1038/s41467-025-60057-0.
The first-ever recent Marburg virus (MARV) outbreak in Tanzania and recent emergences in Rwanda, Ghana and Equatorial Guinea underscore the importance of therapeutic or vaccine development against the virus, for which none are approved. mRNA vaccines were proven successful in a pandemic-response to severe acute respiratory syndrome coronavirus-2, making it an appealing platform to target pathogenic emerging viruses. Here, we develop 1-methyl-pseudouridine-modified mRNA vaccines formulated in lipid nanoparticles (LNP) targeting the glycoproteins (GP) of MARV and the closely-related Ravn virus (RAVV). Vaccination of female guinea pigs elicits robust binding and neutralizing antibodies and confers complete protection against homologous and heterologous virus replication, disease and death. Characterization of antibody responses identifies disparities in the binding and functional profiles between the two viruses and regions in GP that are broadly reactive. The glycan cap is highlighted as an immunoreactive site for orthomarburgviruses, inducing antibody responses that are virus dependent. Profiling the antibody responses against the two viruses provides insight into how antigenic differences may affect the response towards conserved GP regions, which would otherwise be predicted to be cross-reactive, and has implications for the future design of broadly protective vaccines. The results support the use of mRNA-LNPs against pathogens of high consequence.
坦桑尼亚首次出现的马尔堡病毒（MARV）疫情以及卢旺达、加纳和赤道几内亚最近出现的疫情凸显了研发针对该病毒的治疗方法或疫苗的重要性，目前尚无针对该病毒的获批治疗方法或疫苗。信使核糖核酸（mRNA）疫苗在应对严重急性呼吸综合征冠状病毒2的大流行中被证明是成功的，这使其成为针对新出现的致病性病毒的一个有吸引力的平台。在此，我们开发了1-甲基假尿苷修饰的mRNA疫苗，该疫苗被配制在脂质纳米颗粒（LNP）中，靶向马尔堡病毒的糖蛋白（GP）以及密切相关的拉文病毒（RAVV）。对雌性豚鼠进行疫苗接种可引发强烈的结合抗体和中和抗体，并对同源和异源病毒复制、疾病和死亡提供完全保护。抗体反应的特征分析确定了两种病毒之间以及GP中具有广泛反应性的区域在结合和功能方面的差异。聚糖帽被突出显示为正马尔堡病毒属病毒的一个免疫反应位点，可诱导依赖病毒的抗体反应。对针对这两种病毒的抗体反应进行分析，有助于深入了解抗原差异如何影响对保守GP区域的反应，否则预计这些区域会产生交叉反应，这对未来广泛保护性疫苗的设计具有重要意义。研究结果支持使用mRNA-LNP来对抗具有高度危害性的病原体。
