Skip to main content
Erschienen in: Archives of Virology 5/2020

06.03.2020 | Original Article

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

verfasst von: Hai Li, Lei Cao, Yan Zhang, Hu Ren, Peibei Zhao, Wenbo Xu

Erschienen in: Archives of Virology | Ausgabe 5/2020

Einloggen, um Zugang zu erhalten

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.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
2.
Zurück zum Zitat Chanock R, Finberg L (1957) Recovery from infants with respiratory illness of a virus related to chimpanzee coryza agent (CCA). II. Epidemiologic aspects of infection in infants and young children. Am J Hyg 66(3):291–300 Chanock R, Finberg L (1957) Recovery from infants with respiratory illness of a virus related to chimpanzee coryza agent (CCA). II. Epidemiologic aspects of infection in infants and young children. Am J Hyg 66(3):291–300
6.
Zurück zum Zitat Langley JM, Aggarwal N, Toma A, Halperin SA, Shelly M et al (2016) A randomized, controlled, observer-blind phase I study of the safety and immunogenicity of a respiratory syncytial virus vaccine with or without alum adjuvant. J Infect Dis 215:453 Langley JM, Aggarwal N, Toma A, Halperin SA, Shelly M et al (2016) A randomized, controlled, observer-blind phase I study of the safety and immunogenicity of a respiratory syncytial virus vaccine with or without alum adjuvant. J Infect Dis 215:453
9.
Zurück zum Zitat Beran J, Lickliter JD, Schwarz TF, Johnson C, Chu L, Domachowske JB et al (2018) Safety and immunogenicity of 3 formulations of an investigational respiratory syncytial virus vaccine in non-pregnant women: results from two phase II trials. J Infect Dis 217(10):1616CrossRef Beran J, Lickliter JD, Schwarz TF, Johnson C, Chu L, Domachowske JB et al (2018) Safety and immunogenicity of 3 formulations of an investigational respiratory syncytial virus vaccine in non-pregnant women: results from two phase II trials. J Infect Dis 217(10):1616CrossRef
25.
Zurück zum Zitat Kim HW, Canchola JG, Brandt CD, Pyles G, Chanock RM, Jensen K et al (1969) Respiratory syncytial virus disease in infants despite prior administration of antigenic inactivated vaccine. Am J Epidemiol 89(4):422–434CrossRef Kim HW, Canchola JG, Brandt CD, Pyles G, Chanock RM, Jensen K et al (1969) Respiratory syncytial virus disease in infants despite prior administration of antigenic inactivated vaccine. Am J Epidemiol 89(4):422–434CrossRef
26.
Zurück zum Zitat Delgado MF, Coviello S, Monsalvo AC, Melendi GA, Hernandez JZ, Batalle JP et al (2009) Lack of antibody affinity maturation due to poor toll-like receptor stimulation leads to enhanced respiratory syncytial virus disease. Nat Med 15(1):34–41. https://doi.org/10.1038/nm.1894CrossRef Delgado MF, Coviello S, Monsalvo AC, Melendi GA, Hernandez JZ, Batalle JP et al (2009) Lack of antibody affinity maturation due to poor toll-like receptor stimulation leads to enhanced respiratory syncytial virus disease. Nat Med 15(1):34–41. https://​doi.​org/​10.​1038/​nm.​1894CrossRef
37.
Zurück zum Zitat Mapletoft JW, Oumouna M, Kovacs-Nolan J, Latimer L, Mutwiri G, Babiuk LA et al (2008) Intranasal immunization of mice with a formalin-inactivated bovine respiratory syncytial virus vaccine co-formulated with CpG oligodeoxynucleotides and polyphosphazenes results in enhanced protection. J Gen Virol. 89(Pt 1):250–260. https://doi.org/10.1099/vir.0.83300-0CrossRef Mapletoft JW, Oumouna M, Kovacs-Nolan J, Latimer L, Mutwiri G, Babiuk LA et al (2008) Intranasal immunization of mice with a formalin-inactivated bovine respiratory syncytial virus vaccine co-formulated with CpG oligodeoxynucleotides and polyphosphazenes results in enhanced protection. J Gen Virol. 89(Pt 1):250–260. https://​doi.​org/​10.​1099/​vir.​0.​83300-0CrossRef
40.
Zurück zum Zitat Zhao M, Zheng ZZ, Chen M, Modjarrad K, Zhang W, Zhan LT et al (2017) Discovery of a prefusion respiratory syncytial virus F-specific monoclonal antibody that provides greater in Vivo protection than the murine precursor of palivizumab. J Virol 91(15):e00176-00117. https://doi.org/10.1128/jvi.00176-17CrossRef Zhao M, Zheng ZZ, Chen M, Modjarrad K, Zhang W, Zhan LT et al (2017) Discovery of a prefusion respiratory syncytial virus F-specific monoclonal antibody that provides greater in Vivo protection than the murine precursor of palivizumab. J Virol 91(15):e00176-00117. https://​doi.​org/​10.​1128/​jvi.​00176-17CrossRef
43.
Zurück zum Zitat Connors M, Giese NA, Kulkarni AB, Firestone CY, Morse HC, Murphy BR (1994) Enhanced pulmonary histopathology induced by respiratory syncytial virus (RSV) challenge of formalin-inactivated RSV-immunized BALB/c mice is abrogated by depletion of interleukin-4 (IL-4) and IL-10. J Virol 68(8):5321–5325CrossRef Connors M, Giese NA, Kulkarni AB, Firestone CY, Morse HC, Murphy BR (1994) Enhanced pulmonary histopathology induced by respiratory syncytial virus (RSV) challenge of formalin-inactivated RSV-immunized BALB/c mice is abrogated by depletion of interleukin-4 (IL-4) and IL-10. J Virol 68(8):5321–5325CrossRef
Metadaten
Titel
Human respiratory syncytial virus F protein expressed in Pichia pastoris or Escherichia coli induces protective immunity without inducing enhanced respiratory disease in mice
verfasst von
Hai Li
Lei Cao
Yan Zhang
Hu Ren
Peibei Zhao
Wenbo Xu
Publikationsdatum
06.03.2020
Verlag
Springer Vienna
Erschienen in
Archives of Virology / Ausgabe 5/2020
Print ISSN: 0304-8608
Elektronische ISSN: 1432-8798
DOI
https://doi.org/10.1007/s00705-020-04578-7

Weitere Artikel der Ausgabe 5/2020

Archives of Virology 5/2020 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.