Molecular mechanism of antibody neutralization of coxsackievirus A16

Chao Zhang, Caixuan Liu, Jinping Shi, Yalei Wang, Cong Xu, Xiaohua Ye, Qingwei Liu, Xue Li, Weihua Qiao, Yannan Yin, Yao Cong () and Zhong Huang ()
Additional contact information
Chao Zhang: University of Chinese Academy of Sciences
Caixuan Liu: Chinese Academy of Sciences
Jinping Shi: University of Chinese Academy of Sciences
Yalei Wang: University of Chinese Academy of Sciences
Cong Xu: Chinese Academy of Sciences
Xiaohua Ye: University of Chinese Academy of Sciences
Qingwei Liu: University of Chinese Academy of Sciences
Xue Li: University of Chinese Academy of Sciences
Weihua Qiao: University of Chinese Academy of Sciences
Yannan Yin: University of Chinese Academy of Sciences
Yao Cong: Chinese Academy of Sciences
Zhong Huang: University of Chinese Academy of Sciences

Nature Communications, 2022, vol. 13, issue 1, 1-16

Abstract: Abstract Coxsackievirus A16 (CVA16) causes hand, foot and mouth disease in infants and young children. However, no vaccine or anti-viral agent is currently available for CVA16. Here, the functions and working mechanisms of two CVA16-specific neutralizing monoclonal antibodies (MAbs), 9B5 and 8C4, are comprehensively investigated. Both 9B5 and 8C4 display potent neutralization in vitro and prophylactic and therapeutic efficacy in a mouse model of CVA16 infection. Mechanistically, 9B5 exerts neutralization primarily through inhibiting CVA16 attachment to cell surface via blockade of CVA16 binding to its attachment receptor, heparan sulfate, whereas 8C4 functions mainly at the post-attachment stage of CVA16 entry by interfering with the interaction between CVA16 and its uncoating receptor SCARB2. Cryo-EM studies show that 9B5 and 8C4 target distinct epitopes located at the 5-fold and 3-fold protrusions of CVA16 capsids, respectively, and exhibit differential binding preference to three forms of naturally occurring CVA16 particles. Moreover, 9B5 and 8C4 are compatible in formulating an antibody cocktail which displays the ability to prevent virus escape seen with individual MAbs. Together, our work elucidates the functional and structural basis of CVA16 antibody-mediated neutralization and protection, providing important information for design and development of effective CVA16 vaccines and antibody therapies.

Date: 2022
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-022-35575-w Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-35575-w

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-022-35575-w

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().