Conformationally selective biophysical assay for influenza vaccine potency determination

Vaccine
Yingxia WenEthan C Settembre

Abstract

Influenza vaccines are the primary intervention for reducing the substantial health burden from pandemic and seasonal influenza. Hemagglutinin (HA) is the most important influenza vaccine antigen. Subunit and split influenza vaccines are formulated, released for clinical use, and tested for stability based on an in vitro potency assay, single-radial immunodiffusion (SRID), which selectively detects HA that is immunologically active (capable of eliciting neutralizing or hemagglutination inhibiting antibodies in an immunized subject). The time consuming generation of strain-specific sheep antisera and calibrated antigen standards for SRID can delay vaccine release. The limitation in generating SRID reagents was evident during the early days of the 2009 pandemic, prompting efforts to develop more practical, alternative, quantitative assays for immunologically active HA. Here we demonstrate that, under native conditions, trypsin selectively digests HA produced from egg or mammalian cell in monovalent vaccines that is altered by stress conditions such as reduced pH, elevated temperature, or deamidation, leaving native, pre-fusion HA, intact. Subsequent reverse-phase high pressure liquid chromatography (RP-HPLC) can separate trypsin-...Continue Reading

References

Nov 1, 1988·The Journal of General Virology·R W RuigrokD C Wiley
Feb 1, 1986·Virology·S A WhartonD C Wiley
Aug 2, 1972·Nature: New Biology·C M Brand, J J Skehel
Jul 1, 1983·Reviews of Infectious Diseases·J R La MontagneF M Bozeman
Feb 1, 1982·Proceedings of the National Academy of Sciences of the United States of America·J J SkehelD C Wiley
Jul 6, 2000·The Journal of Antimicrobial Chemotherapy·M C Zambon
Aug 31, 2000·Annual Review of Biochemistry·J J Skehel, D C Wiley
Jul 5, 2011·Virology·Fu-Shi QuanSang-Moo Kang

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Citations

Apr 14, 2016·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·John M HickeyDavid B Volkin
May 18, 2017·Biotechnology Journal·Sofia B CarvalhoManuel J T Carrondo
Jan 23, 2018·Influenza and Other Respiratory Viruses·John M Wood, Jerry P Weir
Dec 11, 2017·Biochemistry. Biokhimii︠a︡·N B UstinovA M Kopylov

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