Inactivated or damaged? Comparing the effect of inactivation methods on influenza virions to optimize vaccine production

Autor: Marijke Holtrop, Anke Huckriede, Aurora Signorazzi, José Herrera-Rodriguez, Jacqueline de Vries-Idema
Přispěvatelé: Transplantation Immunology Groningen
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Hemagglutination
viruses
BPL
β-propiolactone
Hemagglutinin Glycoproteins
Influenza Virus
Inactivation
0302 clinical medicine
030212 general & internal medicine
Receptor
Infectivity
biology
Chemistry
NA
neuraminidase
3. Good health
Titer
HAU
hemagglutination units
Infectious Diseases
β-propiolactone
Formaldehyde
Vaccine
Influenza
Inactivation
Influenza A virus
Influenza Vaccines
FA
formaldehyde
Molecular Medicine
TLR
Toll-like receptor
WIV
whole inactivated virus
030231 tropical medicine
Hemagglutinin (influenza)
Virus
Article
TCID50
tissue culture infectious dose (50% thereof)
WHO
World Health Organization
Incubation period
Cell Line
03 medical and health sciences
Formaldehyde
Animals
Humans
General Veterinary
General Immunology and Microbiology
Public Health
Environmental and Occupational Health
Virion
β-propiolactone
Virology
Influenza
Vaccines
Inactivated
Cell culture
biology.protein
RBCs
red blood cells
RNA
ribonucleic acid
Virus Inactivation
ssRNA
single strand RNA
Vaccine
HA
hemagglutinin
Zdroj: Vaccine
Vaccine, 37(12), 1630-1637. ELSEVIER SCI LTD
ISSN: 1873-2518
0264-410X
Popis: Highlights • β-propiolactone (BPL) and formaldehyde (FA) were used to inactivate several influenza virus strains. • BPL abolished the infectivity, FA was unable to completely inactivate the virus. • All methods damaged the binding and fusion capacity; BPL caused greater loss than FA. • FA treatments caused the highest reduction in TLR-7 stimulation. • All the observed effects were strain-dependent.
The vast majority of commercially available inactivated influenza vaccines are produced from egg-grown or cell-grown live influenza virus. The first step in the production process is virus inactivation with β-propiolactone (BPL) or formaldehyde (FA). Recommendations for production of inactivated vaccines merely define the maximal concentration for both reagents, leaving the optimization of the process to the manufacturers. We assessed the effect of inactivation with BPL and FA on 5 different influenza virus strains. The properties of the viral formulation, such as successful inactivation, preservation of hemagglutinin (HA) binding ability, fusion capacity and the potential to stimulate a Toll-like receptor 7 (TLR7) reporter cell line were then assessed and compared to the properties of the untreated virus. Inactivation with BPL resulted in undetectable infectivity levels, while FA-treated virus retained very low infectious titers. Hemagglutination and fusion ability were highly affected by those treatments that conferred higher inactivation, with BPL-treated virus binding and fusing at a lower degree compared to FA-inactivated samples. On the other hand, BPL-inactivated virus induced higher levels of activation of TLR7 than FA-inactivated virus. The alterations caused by BPL or FA treatments were virus strain dependent. This data shows that the inactivation procedures should be tailored on the virus strain, and that many other elements beside the concentration of the inactivating agent, such as incubation time and temperature, buffer and virus concentration, have to be defined to achieve a functional product.
Databáze: OpenAIRE
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