Viruses
National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, Xiamen University, Xiamen, Fujian 361005, China.
Published: July 2019
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 log, mean value of dilution rate) than those inoculated with unstable (unfixed, 8.91 log, < 0.01) or excessively fixed (exce-fixed, 7.28 log, < 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.
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Source |
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6669674 | PMC |
http://dx.doi.org/10.3390/v11070628 | DOI Listing |
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