Highly efficient production of an influenza H9N2 vaccine using MDCK suspension cells

Wu, Yixiao; Jia, Hanjing; Lai, Hanzhang; Liu, Xuping; Tan, Wen‐Song

doi:10.1186/s40643-020-00352-4

Cited by 8 publications

(2 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…An MDCK suspension cell line (ATCC CCL‐34 origin) adapted to grow in suspension in a serum‐free medium (Huang et al, 2011, 2015; Wu et al, 2020), was cultivated in a newly developed chemically defined medium, referred as “Xeno‐CDM” (Shanghai BioEngine Sci‐Tech). For media adaptation to Xeno‐CDM the medium proportion was increased by 25% steps for four passages, with no apparent changes in cell line performance.…”

Section: Methodsmentioning

confidence: 99%

Towards integrated production of an influenza A vaccine candidate with MDCK suspension cells

Bissinger

Marichal-Gallardo

et al. 2021

Biotech & Bioengineering

Self Cite

View full text Add to dashboard Cite

Seasonal influenza epidemics occur both in northern and southern hemispheres every year. Despite the differences in influenza virus surface antigens and virulence of seasonal subtypes, manufacturers are well‐adapted to respond to this periodical vaccine demand. Due to decades of influenza virus research, the development of new influenza vaccines is relatively straight forward. In similarity with the ongoing coronavirus disease 2019 pandemic, vaccine manufacturing is a major bottleneck for a rapid supply of the billions of doses required worldwide. In particular, egg‐based vaccine production would be difficult to schedule and shortages of other egg‐based vaccines with high demands also have to be anticipated. Cell culture‐based production systems enable the manufacturing of large amounts of vaccines within a short time frame and expand significantly our options to respond to pandemics and emerging viral diseases. In this study, we present an integrated process for the production of inactivated influenza A virus vaccines based on a Madin–Darby Canine Kidney (MDCK) suspension cell line cultivated in a chemically defined medium. Very high titers of 3.6 log10(HAU/100 µl) were achieved using fast‐growing MDCK cells at concentrations up to 9.5 × 106 cells/ml infected with influenza A/PR/8/34 H1N1 virus in 1 L stirred tank bioreactors. A combination of membrane‐based steric‐exclusion chromatography followed by pseudo‐affinity chromatography with a sulfated cellulose membrane adsorber enabled full recovery for the virus capture step and up to 80% recovery for the virus polishing step. Purified virus particles showed a homogenous size distribution with a mean diameter of 80 nm. Based on a monovalent dose of 15 µg hemagglutinin (single‐radial immunodiffusion assay), the level of total protein and host cell DNA was 58 µg and 10 ng, respectively. Furthermore, all process steps can be fully scaled up to industrial quantities for commercial manufacturing of either seasonal or pandemic influenza virus vaccines. Fast production of up to 300 vaccine doses per liter within 4–5 days makes this process competitive not only to other cell‐based processes but to egg‐based processes as well.

show abstract

Section: Methodsmentioning

confidence: 99%

Towards integrated production of an influenza A vaccine candidate with MDCK suspension cells

Bissinger

Marichal-Gallardo

et al. 2021

Biotech & Bioengineering

Self Cite

View full text Add to dashboard Cite

show abstract

“…Another study reported generation of an H9 virus-like-particle vaccine using a non-egg-based platform [ 32 ]. Traditionally, vaccines against avian influenza viruses are derived from influenza isolates grown by multiple passage in embryonated chicken eggs; this results in high yield strains, which are then inactivated and delivered with mineral oil adjuvant [ 2 , 33 , 34 , 35 ].…”

Section: Introductionmentioning

confidence: 99%

Protection of SPF Chickens by H9N2 Y439 and G1 Lineage Vaccine against Homologous and Heterologous Viruses

et al. 2023

View full text Add to dashboard Cite

Prior to the identification of low pathogenic avian influenza H9N2 viruses belonging to the Y280 lineage in 2020, Y439 lineage viruses had been circulating in the Republic of Korea since 1996. Here, we developed a whole inactivated vaccine (vac564) by multiple passage of Y439 lineage viruses and then evaluated immunogenicity and protective efficacy in specific-pathogen-free chickens. We found that LBM564 could be produced at high yield in eggs (108.4EID50/0.1 mL; 1024 hemagglutinin units) and was immunogenic (8.0 ± 1.2 log2) in chickens. The vaccine showed 100% inhibition of virus in the cecal tonsil with no viral shedding detected in either oropharyngeal or cloacal swabs after challenge with homologous virus. However, it did not induce effective protection against challenge with heterologous virus. An imported commercial G1 lineage vaccine inhibited viral replication against Y280 and Y439 lineage viruses in major tissues, although viral shedding in oropharyngeal and cloacal swabs was observed up until 5 dpi after exposure to both challenge viruses. These results suggest that a single vaccination with vac564 could elicit immune responses, showing it to be capable of protecting chickens against the Y439 lineage virus. Thus, our results suggest the need to prepare suitable vaccines for use against newly emerging and re-emerging H9N2 viruses.

show abstract

Influenza Vaccine: An Engineering Vision from Virological Importance to Production

Demirden

Alptekin

Kimiz‐Gebologlu

et al. 2022

Biotechnol Bioproc E

View full text Add to dashboard Cite

According to data from the World Health Organization (WHO) every year, millions of people are affected by flu. Flu is a disease caused by influenza viruses. For preventing this, seasonal influenza vaccinations are widely considered the most efficient way to protect against the negative effects of the flu. To date, there is no “one-size-fits-all” vaccine that can be effective all over the world to protect against all seasonal or pandemic influenza virus types. Because influenza virus transforms its genetic structure and it can emerges as immunogenically new (antigenic drift) which causes epidemics or new virus subtype (antigenic shift) which causes pandemics. As a result, annual revaccination or new subtype viral vaccine development is required. Currently, three types of vaccines (inactivated, live attenuated, and recombinant) are approved in different countries. These can be named “conventional influenza vaccines” and their production are based on eggs or cell culture. Although, there is good effort to develop new influenza vaccines for broader and longer period of time protection. In this sense these candidate vaccines are called “universal influenza vaccines”. In this article, after we mentioned the short history of flu then virus morphology and infection, we explained the diseases caused by the influenza virus in humans. Afterward, we explained in detail the production methods of available influenza vaccines, types of bioreactors used in cell culture based production, conventional and new vaccine types, and development strategies for better vaccines.

show abstract

Highly efficient production of an influenza H9N2 vaccine using MDCK suspension cells

Cited by 8 publications

References 46 publications

Towards integrated production of an influenza A vaccine candidate with MDCK suspension cells

Towards integrated production of an influenza A vaccine candidate with MDCK suspension cells

Protection of SPF Chickens by H9N2 Y439 and G1 Lineage Vaccine against Homologous and Heterologous Viruses

Influenza Vaccine: An Engineering Vision from Virological Importance to Production

Contact Info

Product

Resources

About