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Human respiratory syncytial virus F protein expressed in Pichia pastoris or Escherichia coli induces protective immunity without inducing enhanced respiratory disease in mice

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Abstract

Human respiratory syncytial virus (hRSV) is the primary cause of severe respiratory tract disease in children and infants as well as in elderly and immunocompromised adults. The fusion protein (F) of hRSV is the major antigen eliciting a neutralizing antibody response and protective immunity in the host, especially those recognizing the prefusion F protein (pre-F). In this study, we made genetic constructs for expression of a recombinant prefusion F protein in Pichia pastoris GS115, called RGF. Using Escherichia coli BL21, we expressed the pre-F and postfusion F protein (Post-F), called RBF and Post-RBF, respectively. RGF and RBF showed high affinity for 5C4, a highly potent monoclonal antibody specific for pre-F. We studied the immunogenicity of RGF and RBF in mice. Compared to mice immunized with formalin-inactivated RSV (FI-RSV), mice immunized with RGF or RBF exhibited superior protective immunity, which was confirmed by serum neutralizing activity and viral clearance after challenge. As judged from the IgG1/IgG2a ratios and numbers of IFN-γ- and IL-4-secreting cells, RGF or RBF with alum adjuvant induced a balanced Th1-biased immune response and produced no signs of enhanced respiratory disease (ERD) upon hRSV challenge. In addition, the immunogenicity and protective efficacy of RGF were superior to those of RBF in mice. Therefore, RGF represents a potential vaccine candidate for the prevention of human infection with hRSV.

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Data availability

All data included in this study are available upon request from the corresponding author.

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Acknowledgements

We thank Professor Ningshao Xia for generously supplying the 5C4 antibody.

Funding

This work was supported by the Key Technologies R&D Program of the National Ministry of Science (2018ZX10713002 and 2018ZX10713001-003).

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Author notes

  1. Hai Li and Lei Cao contributed equally to this article.

Authors and Affiliations

  1. NHC Key Laboratory of Medical Virology and Viral Diseases, National Institute for Viral Disease Control and Prevention, China CDC, Beijing, China

    Hai Li, Lei Cao, Yan Zhang, Hu Ren & Wenbo Xu

  2. Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Inner Mongolia Medical University, Hohhot, China

    Peibei Zhao

  3. Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, China

    Wenbo Xu

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  1. Hai Li
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  3. Yan Zhang
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Contributions

HL, YZ and WBX designed the study and prepared the manuscript. HL, LC and PBZ expressed and purified the protein. HL and HR performed the animal experiments and analyzed the data. All authors read and approved the final manuscript.

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Correspondence to Wenbo Xu.

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Li, H., Cao, L., Zhang, Y. et al. Human respiratory syncytial virus F protein expressed in Pichia pastoris or Escherichia coli induces protective immunity without inducing enhanced respiratory disease in mice. Arch Virol 165, 1057–1067 (2020). https://doi.org/10.1007/s00705-020-04578-7

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