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Open AccessArticle

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

1
National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, Xiamen University, Xiamen, Fujian 361005, China
2
State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, Fujian 361005, China
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this article.
Viruses 2019, 11(7), 628; https://doi.org/10.3390/v11070628
Received: 12 April 2019 / Revised: 1 July 2019 / Accepted: 6 July 2019 / Published: 8 July 2019
(This article belongs to the Section Animal Viruses)
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Abstract

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. View Full-Text
Keywords: respiratory syncytial virus; fusion protein; pre-fusion conformation; antigenic sites; fixatives; formaldehyde; stabilization; protection; pulmonary inflammation respiratory syncytial virus; fusion protein; pre-fusion conformation; antigenic sites; fixatives; formaldehyde; stabilization; protection; pulmonary inflammation
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Zhang, W.; Zhang, L.-J.; Zhan, L.-T.; Zhao, M.; Wu, G.-H.; Si, J.-Y.; Chen, L.; Lin, X.; Sun, Y.-P.; Lin, M.; Yu, C.; Fang, M.-J.; Wang, Y.-B.; Zheng, Z.-Z.; Xia, N.-S. The Optimal Concentration of Formaldehyde is Key to Stabilizing the Pre-Fusion Conformation of Respiratory Syncytial Virus Fusion Protein. Viruses 2019, 11, 628.

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