The Optimal Concentration of Formaldehyde is Key to Stabilizing the Pre-Fusion Conformation of Respiratory Syncytial Virus Fusion Protein

Autor:	Zizheng Zheng, Junyu Si, Chao Yu, Zhang Lujing, Wei Zhang, Yong-Peng Sun, Lu-Ting Zhan, Chen Li, Xue Lin, Guang-Hua Wu, Yingbin Wang, Mujin Fang, Min Lin, Ningshao Xia, Min Zhao
Rok vydání:	2019
Předmět:	0301 basic medicine Immunogen Protein Conformation respiratory syncytial virus 030106 microbiology lcsh:QR1-502 Respiratory Syncytial Virus Infections Antibodies Viral pulmonary inflammation antigenic sites Article lcsh:Microbiology Neutralization Virus Cell Line Epitopes Mice 03 medical and health sciences chemistry.chemical_compound Antigen Virology fusion protein Animals Paraformaldehyde Neutralizing antibody Mice Inbred BALB C pre-fusion conformation fixatives biology Vaccination protection Antibodies Neutralizing Fusion protein Respiratory Syncytial Viruses stabilization Disease Models Animal Titer 030104 developmental biology Infectious Diseases Vaccines Inactivated chemistry Immunoglobulin G biology.protein formaldehyde Immunization Viral Fusion Proteins
Zdroj:	Viruses, Vol 11, Iss 7, p 628 (2019) Viruses Volume 11 Issue 7
ISSN:	1999-4915
DOI:	10.3390/v11070628
Popis:	Background: To date, there is no licensed vaccine available to prevent respiratory syncytial virus (RSV) infection. The valuable pre-fusion conformation of the fusion protein (pre-F) is prone to lose high neutralizing antigenic sites. The goals of this study were to stabilize pre-F protein by fixatives and try to find the possibility of developing an inactivated RSV vaccine. Methods: The screen of the optimal fixative condition was performed with flow cytometry. BALB/c mice were immunized intramuscularly with different immunogens. The serum neutralizing antibody titers of immunized mice were determined by neutralization assay. The protection and safety of these immunogens were assessed. Results: Fixation in an optimal concentration of formaldehyde (0.0244%–0.0977%) or paraformaldehyde (0.0625%–1%) was able to stabilize pre-F. Additionally, BALB/c mice inoculated with optimally stabilized pre-F protein (opti-fixed) induced a higher anti-RSV neutralization (9.7 log2, mean value of dilution rate) than those inoculated with unstable (unfixed, 8.91 log2, p < 0.01) or excessively fixed (exce-fixed, 7.28 log2, p < 0.01) pre-F protein. Furthermore, the opti-fixed immunogen did not induce enhanced RSV disease. Conclusions: Only the proper concentration of fixatives could stabilize pre-F and the optimal formaldehyde condition provides a potential reference for development of an inactivated RSV vaccine.
Databáze:	OpenAIRE
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