Chan Andy Kwan Pui, Liu Liting, Morgenlander William R, Thakar Manjusha, Peart Akindele Nadine A, Brockhurst Jacqueline, Ghimire Shristi, Bartlett Maggie L, Metcalf Pate Kelly A, Chu Victor C, Vermillion Meghan S, Porter Danielle P, Cihlar Tomas, Mina Michael J, Larman H Benjamin, Griffin Diane E
W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
Graduate Program in Immunology.
JCI Insight. 2025 Apr 22;10(11). doi: 10.1172/jci.insight.190740. eCollection 2025 Jun 9.
Measles remains one of the most important causes of worldwide morbidity and mortality in children. Measles virus (MeV) replicates extensively in lymphoid tissue, and most deaths are due to other infectious diseases associated with MeV-induced loss of circulating antibodies to other pathogens. To determine whether remdesivir, a broad-spectrum direct-acting antiviral, affects MeV-induced loss of antibody to other pathogens, we expanded the VirScan technology to detect antibodies to both human and macaque pathogens. We measured the antibody reactivity to MeV and non-MeV viral peptides using plasma from MeV-infected macaques that received remdesivir either as postexposure prophylaxis (PEP) (d3-d14) or as late treatment (LT) (d11-d22) in comparison with macaques that were not treated. Remdesivir PEP, but not LT, limited the loss of antibody to non-MeV pathogens. Remdesivir PEP also limited the antibody response to MeV with a decrease in both the magnitude and breadth of the epitopes recognized. LT had little effect on the magnitude of the MeV-specific antibody response but affected the breadth of the response. Therefore, early, but not late, treatment of measles with the direct-acting antiviral remdesivir prevents the loss of antibody to other pathogens but decreases the response to MeV.
麻疹仍然是全球儿童发病和死亡的最重要原因之一。麻疹病毒(MeV)在淋巴组织中广泛复制,大多数死亡是由于与MeV诱导的针对其他病原体的循环抗体丧失相关的其他传染病。为了确定广谱直接作用抗病毒药物瑞德西韦是否会影响MeV诱导的针对其他病原体的抗体丧失,我们扩展了VirScan技术以检测针对人类和猕猴病原体的抗体。我们使用来自接受瑞德西韦作为暴露后预防(PEP)(第3天至第14天)或晚期治疗(LT)(第11天至第22天)的MeV感染猕猴的血浆,测量了对MeV和非MeV病毒肽的抗体反应性,并与未接受治疗的猕猴进行了比较。瑞德西韦PEP而非LT限制了针对非MeV病原体的抗体丧失。瑞德西韦PEP还限制了对MeV的抗体反应,识别的表位的大小和广度均降低。LT对MeV特异性抗体反应的大小影响不大,但影响了反应的广度。因此,用直接作用抗病毒药物瑞德西韦早期而非晚期治疗麻疹可防止针对其他病原体的抗体丧失,但会降低对MeV的反应。