Computational redesign of human respiratory syncytial virus epitope as therapeutic peptide vaccines against pediatric pneumonia

  • Xiangxiang Shi
  • Jun Zheng
  • Tingting Yan
Original Paper


Human respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in infants and young children. Here, the RSV fusion (F) glycoprotein epitope FFL was redesigned based on its complex crystal structure with motavizumab, an mAb drug in development for the prevention of RSV infections, aiming to obtain therapeutic peptide vaccines with high affinity to induce RSV-specific neutralizing antibodies. Computational modeling and analysis found that only a small region covering the helix-turn-helix (HTH) motif of FFL can directly interact with motavizumab and confer stability and specificity to the complex system, while the rest of the epitope primarily serves as a structural scaffold that stabilizes the HTH conformation of motavizumab-binding site. Molecular dynamics simulations revealed a large flexibility and intrinsic disorder for the isolated linear HTH peptide, which would incur a considerable entropy penalty upon binding to motavizumab. In this respect, the FFL epitope was redesigned by truncation, mutation, and cyclization to derive a number of small cyclic peptide immunogens. We also employed in vitro fluorescence-based assays to demonstrate that the linear epitope peptide has no observable affinity to motavizumab, whereas redesigned versions of the peptide can bind with a moderate or high potency.

Graphical abstract

Computationally modeled complex structure of RSV F glycoprotein with motavizumab and zoom up of the complex binding site.


Respiratory syncytial virus Fusion glycoprotein epitope Rational peptide vaccine design Pediatric pneumonia 


Compliance with ethical standards

Conflict of interest

The authors report no conflicts of interest.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of PediatricsHuai’an Affiliated Hospital of Xuzhou Medical University, The Second People’s Hospital of Huai’anHuai’anPeople’s Republic of China
  2. 2.Department of PediatricsCentral Hospital of Shanghai Minhang DistrictShanghaiPeople’s Republic of China

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