title: Analytical technologies for influenza virus-like particle candidate vaccines: challenges and emerging approaches.
abstract: Influenza virus-like particle vaccines are one of the most promising ways to respond to the threat of future influenza pandemics. VLPs are composed of viral antigens but lack nucleic acids making them non-infectious which limit the risk of recombination with wild-type strains. By taking advantage of the advancements in cell culture technologies, the process from strain identification to manufacturing has the potential to be completed rapidly and easily at large scales. After closely reviewing the current research done on influenza VLPs, it is evident that the development of quantification methods has been consistently overlooked. VLP quantification at all stages of the production process has been left to rely on current influenza quantification methods (i.e. Hemagglutination assay (HA), Single Radial Immunodiffusion assay (SRID), NA enzymatic activity assays, Western blot, Electron Microscopy). These are analytical methods developed decades ago for influenza virions and final bulk influenza vaccines. Although these methods are time-consuming and cumbersome they have been sufficient for the characterization of final purified material. Nevertheless, these analytical methods are impractical for in-line process monitoring because VLP concentration in crude samples generally falls out of the range of detection for these methods. This consequently impedes the development of robust influenza-VLP production and purification processes. Thus, development of functional process analytical techniques, applicable at every stage during production, that are compatible with different production platforms is in great need to assess, optimize and exploit the full potential of novel manufacturing platforms.
authors: National Research Council Canada, Vaccine Program-Human Health Therapeutics Portfolio, 6100 Royalmount Avenue, Montreal, Québec H4P 2R2, Canada.
authors: Christine M
authors: CM
authors: Thompson
authors: Emma
authors: E
authors: Petiot
authors: Alexandre
authors: A
authors: Lennaertz
authors: Olivier
authors: O
authors: Henry
authors: Amine A
authors: AA
authors: Kamen
mesh_terms: D000956:Antigens, Viral / Q000032:analysis*; D001709:Biotechnology / Q000592:standards*; D006801:Humans; D007252:Influenza Vaccines / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification* / Q000592:standards; D013678:Technology, Pharmaceutical / Q000592:standards*; D058425:Vaccines, Virus-Like Particle / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification* / Q000592:standards
chemical_list: D000956:Antigens, Viral; D007252:Influenza Vaccines; D058425:Vaccines, Virus-Like Particle
references: J Virol. 2007 Jul;81(13):7111-23
references: 17475660
references: Vaccine. 2003 May 1;21(16):1776-9
references: 12686093
references: J Infect Dis. 2009 Jul 15;200(2):181-90
references: 19505256
references: Vaccine. 2010 Oct 4;28(42):6821-31
references: 20727393
references: Mol Biotechnol. 2010 Jul;45(3):226-34
references: 20300881
references: Anal Biochem. 2000 May 1;280(2):291-300
references: 10790313
references: PLoS One. 2009;4(3):e4667
references: 19252744
references: J Biol Stand. 1977;5(3):237-47
references: 408355
references: Cytometry A. 2005 Jun;65(2):140-7
references: 15830378
references: Med Microbiol Immunol. 2009 Aug;198(3):175-83
references: 19543913
references: J Gen Virol. 2010 Sep;91(Pt 9):2322-30
references: 20505010
references: Curr Protoc Microbiol. 2006 Dec;Chapter 15:Unit 15G.1
references: 18770580
references: BMC Biotechnol. 2011 Sep 01;11:84
references: 21884612
references: J Exp Med. 1942 Jan 1;75(1):49-64
references: 19871167
references: Nature. 1967 Sep 16;215(5107):1287-8
references: 6052734
references: J Virol Methods. 2011 Dec;178(1-2):201-8
references: 21963394
references: Dev Biol Stand. 1999;98:183-8; discussion 197
references: 10494972
references: J Chromatogr A. 2006 Aug 11;1123(2):225-32
references: 16677659
references: J Virol. 2001 Jul;75(13):6154-65
references: 11390617
references: Biotechnol Bioeng. 2009 Feb 15;102(3):845-55
references: 18958863
references: PLoS One. 2010 Mar 22;5(3):e9784
references: 20339535
references: Biotechnol J. 2010 Jan;5(1):17-23
references: 20041443
references: Trends Biotechnol. 2012 Apr;30(4):216-24
references: 22172689
references: Vaccine. 2011 Aug 11;29(35):5911-8
references: 21723354
references: Anal Chem. 2008 Feb 15;80(4):1067-72
references: 18198894
references: Viral Immunol. 2005;18(1):244-51
references: 15802970
references: Bull World Health Organ. 1975;52(2):223-31
references: 816480
references: Vaccine. 2008 Nov 11;26(48):6068-76
references: 19007587
references: Anal Biochem. 2008 May 15;376(2):163-72
references: 18342613
references: J Virol Methods. 2004 Dec 1;122(1):9-15
references: 15488615
references: Science. 2009 May 8;324(5928):700-2
references: 19423781
references: Anal Chem. 2009 Nov 15;81(22):9425-32
references: 19803497
references: Biotechnol Bioeng. 2007 Apr 1;96(5):932-44
references: 16937411
references: PLoS One. 2011;6(10):e26335
references: 22039464
references: J Vis Exp. 2011 Apr 04;(50):
references: 21490585
references: Biotechnol Prog. 2011 Mar-Apr;27(2):547-54
references: 21302365
references: Antiviral Res. 2009 Dec;84(3):215-24
references: 19772876
references: J Virol Methods. 2012 Jun;182(1-2):70-5
references: 22460038
references: Vaccine. 2008 Jun 19;26(26):3352-61
references: 18468740
references: Crit Care. 2010;14(2):218
references: 20497595
references: J Gen Microbiol. 1955 Apr;12(2):241-7
references: 14367748
references: J Virol Methods. 2007 Sep;144(1-2):122-32
references: 17586059
references: J Virol. 2007 Apr;81(7):3514-24
references: 17251294
references: Vaccine. 2011 Apr 18;29(18):3377-89
references: 21397719
references: Vaccine. 2005 Dec 30;23(50):5751-9
references: 16143432
references: Vaccine. 2006 Apr 12;24(16):3137-44
references: 16490287
references: Viral Immunol. 2011 Aug;24(4):311-9
references: 21830902
references: J Gen Microbiol. 1954 Jun;10(3):457-64
references: 13174769
references: J Virol Methods. 2011 May;173(2):364-73
references: 21419169
references: Analyst. 2011 Aug 7;136(15):3083-90
references: 21666913
references: Vaccine. 2009 Feb 25;27(9):1468-77
references: 19110022
references: Vaccine. 2007 May 10;25(19):3871-8
references: 17337102
references: Vaccine. 2012 Jul 6;30(32):4762-70
references: 22643214
references: PLoS One. 2010 Dec 22;5(12):e15559
references: 21203523
references: Virus Res. 2009 Aug;143(2):140-6
references: 19374929
references: Expert Rev Vaccines. 2009 Apr;8(4):435-45
references: 19348559
references: Vaccine. 2010 Jan 8;28(3):759-66
references: 19857452
references: Vaccine. 2010 Aug 16;28(36):5774-84
references: 20621113
references: Nat Protoc. 2010 Jan;5(1):14-9
references: 20010723
references: Vaccine. 2012 May 14;30(23):3413-22
references: 22465746
references: Plant Biotechnol J. 2008 Dec;6(9):930-40
references: 19076615
references: J Virol Methods. 2011 Jan;171(1):111-6
references: 20970458
references: Plant Biotechnol J. 2010 Jun;8(5):607-19
references: 20199612
references: Vaccine. 2008 Oct 3;26(42):5393-9
references: 18706956
references: PLoS One. 2012;7(8):e42363
references: 22879951
references: Vaccine. 2008 May 12;26(20):2510-20
references: 18440105
references: Anal Chim Acta. 2008 Aug 8;623(1):66-75
references: 18611459
references: PLoS One. 2012;7(12):e51559
references: 23236516
references: Biologicals. 2008 May;36(3):145-61
references: 18561375
references: Virol J. 2006 Sep 03;3:70
references: 16948862