An inactivated poliovirus vaccine using Sabin strains produced on the serum-free PER.C6® cell culture platform is immunogenic and safe in a non-human primate model

Abstract

BackgroundThe World Health Organization recommends the development of affordable next-generation inactivated poliovirus vaccines (IPV) using attenuated poliovirus Sabin strains. Previously, we introduced a novel PER.C6® cell culture platform, which allows for high yield production of an affordable trivalent Sabin IPV vaccine.MethodsImmunogenicity and safety of this novel PER.C6®-based Sabin-IPV (sIPV) was assessed in rats and non-human primates (NHPs). NHPs received one of four different dose dilutions vaccine according to current human schedule (three prime-immunizations and one boost immunization). For comparison, NHPs received commercially available reference Salk IPV or sIPV.ResultsDose-dependent immunogenicity and good tolerability was observed for the PER.C6®-based sIPV formulations in rats and NHPs. In NHPs, the lowest tested dose that induced anti-Sabin virus-neutralizing antibody titers that were non-inferior to commercial sIPV after three immunizations was 5-7.5-25 D-antigen units for type 1, 2 and 3 respectively.DiscussionPER.C6®-based sIPV induced comparable immunogenicity to commercial Salk IPV and sIPV vaccines in NHPs. Together with the absence of any preclinical safety signals, these data warrant further testing in clinical trials. sIPV produced on the PER.C6® cell platform could be one solution to the need for an affordable and immunogenic IPV to achieve and maintain global polio eradication.

Safety and immunogenicity of a new Sabin inactivated poliovirus vaccine candidate produced on the PER.C6® cell-line: a phase 1 randomized controlled trial in adults

“…23 The IPV evaluated here is based on the safer-tomanufacture Sabin poliovirus strains and the PER.C6® platform. This platform supports a high productivity of polioviruses, [27][28][29] which showed immunogenicity in preclinical models. 29 We describe here the first clinical assessment of the PER.C6® sIPV in adult volunteers.…”

Polio and Its Epidemiology

“…Substitution of Sabin strains or the new candidate OPV strains for IPV strains in a new inactivated polio vaccine (sIPV) to provide safe, affordable next-generation inactivated poliovirus vaccines is another alternative that is currently being explored [80,82,248,251,[253][254][255]. Chumakov et al [82] suggested four possible solutions to the problem of lower stability and immunogenicity of Sabin OPV strains when inactivated to be used for IPV: (1) increase antigen content to a level that would ensure adequate seroconversion (disadvantages: it requires growing greater quantities of virus made more difficult since yields of Sabin strains are lower than wildtype viruses; increases costs); (2) stimulate immunogenicity with adjuvants; (3) explore use of alternative inactivating agents that do not damage antigens as much as formaldehyde; and (4) make IPV from new, genetically stable, nonpathogenic, hyperattenuated engineered poliovirus strains with antigenic structures identical to the currently used wild-type strains [34,256].…”

“…Differences in antigenic structure of inactivated polio vaccines made from Sabin live attenuated and wild-type poliovirus strains effected equivalency of vaccine potency assays used to measure the D-antigen content of the vaccines [255]. This required development of new international standard, IS 12/104, for sIPV [80,81].…”

“…"Strictly spoken, the D-antigen unit represents two entities (antigenic content and immunogenic content) which are equivalent for WT-IPV but are different for Sabin-IPV" in [71]. Differences between results for D-antigen content for IPV strains and for OPV strains used in preparing IPV (sIPV) required that a new international standard be formulated [71,[80][81][82]. It is good to keep in mind the observation by Salk et al [83] that "the essential factor in the preparation of such a [polio] vaccine is the inclusion of a sufficient mass of the immunizing antigen, for each of the three antigenic types of poliovirus, to induce the formation of humoral antibody and/or immunologic memory after the first dose.…”

In-Vitro Inactivation of Sabin-Polioviruses for Development of Safe and Effective Polio Vaccine

“…Finally, Optimization of the vaccine manufacturing process via the usage of less infectious virus strains became a priority to allow IPV production in middle- and low-income countries due to the unacceptable biosafety risks accompanied with conventional IPV production. IPV developed from live-attenuated Sabin strains (sIPV) was a reasonable alternative and many studies proved its efficacy and affordability [ 11 , 12 , 13 , 14 ]. In 2012, manufacturers in Japan and China were licensed for production and marketing of Sabin-IPV and this vaccine is used there extensively.…”