PER.C6® cells as a serum-free suspension cell platform for the production of high titer poliovirus: A potential low cost of goods option for world supply of inactivated poliovirus vaccine

Sanders, Barbara P.; Edo-Matas, Diana; Custers, Jerome; Koldijk, Martin; Klaren, Vincent; Turk, Marije; Luitjens, Alfred; Bakker, Wilfried A.M.; Uytdehaag, Fons G. C. M.; Goudsmit, Jaap; Lewis, John A.; Schuitemaker, Hanneke

doi:10.1016/j.vaccine.2012.10.070

Cited by 47 publications

(46 citation statements)

References 32 publications

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“…This indicated that growth at low and physiological temperatures was similar for both parental (Brunhilde and Mahoney) and derived attenuated (Brunenders and Sabin 1) strains. These results are in line with previously published data with respect to titres and D-antigen production of PV strains on a PER.C6 platform, and also at a larger scale in 2 l bioreactors (Sanders et al, 2013).…”

Section: Brunenders Displays In Vitro Growth Kinetics Comparable To Osupporting

confidence: 93%

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Brunenders: a partially attenuated historic poliovirus type I vaccine strain

Sanders

Liu

Brandjes

et al. 2015

Journal of General Virology

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Brunenders, a type I poliovirus (PV) strain, was developed in 1952 by J. F. Enders and colleagues through serial in vitro passaging of the parental Brunhilde strain, and was reported to display partial neuroattenuation in monkeys. This phenotype of attenuation encouraged two vaccine manufacturers to adopt Brunenders as the type I component for their inactivated poliovirus vaccines (IPVs) in the 1950s, although today no licensed IPV vaccine contains Brunenders. Here we confirmed, in a transgenic mouse model, the report of Enders on the reduced neurovirulence of Brunenders. Although dramatically neuroattenuated relative to WT PV strains, Brunenders remains more virulent than the attenuated oral vaccine strain, Sabin 1. Importantly, the neuroattenuation of Brunenders does not affect in vitro growth kinetics and in vitro antigenicity, which were similar to those of Mahoney, the conventional type I IPV vaccine strain. We showed, by full nucleotide sequencing, that Brunhilde and Brunenders differ at 31 nucleotides, eight of which lead to amino acid changes, all located in the capsid. Upon exchanging the Brunenders capsid sequence with that of the Mahoney capsid, WT neurovirulence was regained in vivo, suggesting a role for the capsid mutations in Brunenders attenuation. To date, as polio eradication draws closer, the switch to using attenuated strains for IPV is actively being pursued. Brunenders preceded this novel strategy as a partially attenuated IPV strain, accompanied by decades of successful use in the field. Providing data on the attenuation of Brunenders may be of value in the further construction of attenuated PV strains to support the grand pursuit of the global eradication of poliomyelitis.

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Section: Brunenders Displays In Vitro Growth Kinetics Comparable To Osupporting

confidence: 93%

“…Infections were incubated at either 30 or 37 uC and harvested at various time points post-inoculation. Titrations by TCID 50 assay and D-antigen ELISA of viral harvests were performed as described previously (Sanders et al, 2013).…”

Section: Methodsmentioning

confidence: 99%

Brunenders: a partially attenuated historic poliovirus type I vaccine strain

Sanders

Liu

Brandjes

et al. 2015

Journal of General Virology

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“…Снижение за-трат может быть достигнуто благодаря увеличению выхода вирусных частиц путем введения новых производственных процессов и клеточных субстра-тов. По опубликованным данным, использование суспензионных культур клеток PerC6 в бессыворо-точной среде позволяет клеткам расти в услови-ях значительно большей плотности и обеспечить более высокий выход вируса [120]. Еще одним способом снизить стоимость производства вак-цины является использование альтернативных путей введения, что приведет к увеличению им-муногенности и позволит снизить вводимую дозу.…”

Section: новое поколение полиовакцинunclassified

Polio Vaccines: Present and Future

Chumakov¹,

Ишмухаметов²

2018

Epidemiology and Vaccine Prevention

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“…Cost reduction could be achieved by increasing the yields of virus by introducing new manufacturing processes and cell substrates. It has been reported that use of suspension cultures of PerC6 cells in serum-free medium allows cells to grow to a much higher densities and results in a higher virus yields (Sanders et al 2013). Another way to reduce vaccine cost is to use alternative routes of delivery that would increase immunogenicity and allow dose-sparing.…”

Section: New Generation Of Polio Vaccinesmentioning

confidence: 99%

Current Status and Future of Polio Vaccines and Vaccination

Chumakov

2014

Novel Technologies for Vaccine Development

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The history of polio vaccines and their use illustrates the concept of evolution of vaccines driven by changing epidemiological and socioeconomic conditions. The development of two vaccines against poliomyelitis-inactivated Salk vaccine (IPV) and live oral Sabin vaccine (OPV)-is among the most consequential achievements of prophylactic medicine of the past century. Each with their own strengths and weaknesses, they were used over the past 50 years in different settings and different regimens and combinations. This resulted in virtual elimination of the disease in almost the entire world with the exception of a few countries. Continuation of the eradication campaign coordinated by WHO may soon result in complete cessation of wild poliovirus transmission, and poliovirus may join smallpox virus in the club of extinct pathogens. However, unlike smallpox vaccination that was stopped after the interruption of virus circulation, vaccination against poliomyelitis will have to continue into the foreseeable future, due to significant differences in the nature and epidemiology of the viruses. This chapter reviews the reasons for the need to maintain high population immunity against polioviruses, makes the case for developing a new generation of polio vaccines, and discusses their desirable properties as well as new vaccine technologies that could be used to create polio vaccines for the post-eradication environment.

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PER.C6® cells as a serum-free suspension cell platform for the production of high titer poliovirus: A potential low cost of goods option for world supply of inactivated poliovirus vaccine

Cited by 47 publications

References 32 publications

Brunenders: a partially attenuated historic poliovirus type I vaccine strain

Brunenders: a partially attenuated historic poliovirus type I vaccine strain

Polio Vaccines: Present and Future

Current Status and Future of Polio Vaccines and Vaccination

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