Abstract
AbstractEchovirus 30 (E30), a serotype of Enterovirus B (EV-B), recently emerged as a major causative agent of aseptic meningitis worldwide. E30 is particularly devastating in the neonatal population and currently no vaccine or antiviral therapy is available. Here we characterize two highly potent E30-specific monoclonal antibodies, 6C5 and 4B10, which efficiently block binding of the virus to its attachment receptor CD55 and uncoating receptor FcRn. Combinations of 6C5 and 4B10 augment the sum of their individual anti-viral activities. High-resolution structures of E30-6C5-Fab and E30-4B10-Fab define the location and nature of epitopes targeted by the antibodies. 6C5 and 4B10 engage the capsid loci at the north rim of the canyon and in-canyon, respectively. Notably, these regions exhibit antigenic variability across EV-Bs, highlighting challenges in development of broad-spectrum antibodies. Our structures of these neutralizing antibodies of E30 are instructive for development of vaccines and therapeutics against EV-B infections.
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry
Reference61 articles.
1. Manki, A., Oda, M. & Seino, Y. [Neurologic diseases of enterovirus infections: polioviruses, coxsackieviruses, echoviruses, and enteroviruses type 68-72]. Nippon Rinsho. 55, 849–854 (1997)
2. Broberg, E. K., Simone, B. & Jansa, J., The Eu Eea Member State Contributors. Upsurge in echovirus 30 detections in five EU/EEA countries, April to September, 2018. Eur. Surveill. 23, 1800537 (2018).
3. Niu, S. et al. Molecular and structural basis of Echovirus 11 infection by using the dual-receptor system of CD55 and FcRn. Chin. Sci. Bull. 65, 67–79 (2020).
4. Maruo, Y. et al. Outbreak of aseptic meningitis caused by echovirus 30 in Kushiro, Japan in 2017. J. Clin. Virol. 116, 34–38 (2019).
5. Pino-Ramírez, R. M., Pertierra-Cortada, A., Iriondo-Sanz, M., Krauel-Vidal, X. & Muñoz-Almagro, C. Neonatal echovirus 30 infection associated with severe hepatitis in twin neonates. Pediatr. Infect. Dis. J. 27, 88 (2008).
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