Risks associated with the use of live-attenuated vaccine poliovirus strains and the strategies for control and eradication of paralytic poliomyelitis

Pliaka, Vaia; Kyriakopoulou, Zaharoula; Markoulatos, Panayotis

doi:10.1586/erv.12.28

Cited by 65 publications

(59 citation statements)

References 182 publications

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“…3a, Table 3). Some of the known attenuating mutations in the Sabin 1, CHAT and Cox strains, all attenuated derivatives of Mahoney, are also found in the capsid region (Martín & Minor, 2002;Pliaka et al, 2012). In particular, mutation in aa 138 of VP2 (VP2-138) and VP2-142, which were also observed here, has been implicated to play a role in the attenuation of the CHAT and Cox strains.…”

Section: Genetic Characterization Of Brunenderssupporting

confidence: 65%

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: Genetic Characterization Of Brunenderssupporting

confidence: 65%

Brunenders: a partially attenuated historic poliovirus type I vaccine strain

Sanders

Liu

Brandjes

et al. 2015

Journal of General Virology

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“…Both live attenuated and inactivated whole virus vaccines have achieved successful control of poliovirus [60]. Thus, it is logical to believe that EV71, which is similar to poliovirus, can also be controlled with by vaccination.…”

Section: Reviewmentioning

confidence: 99%

Animal models of enterovirus 71 infection: applications and limitations

Wang

2014

J Biomed Sci

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Human enterovirus 71 (EV71) has emerged as a neuroinvasive virus that is responsible for several outbreaks in the Asia-Pacific region over the past 15 years. Appropriate animal models are needed to understand EV71 neuropathogenesis better and to facilitate the development of effective vaccines and drugs. Non-human primate models have been used to characterize and evaluate the neurovirulence of EV71 after the early outbreaks in late 1990s. However, these models were not suitable for assessing the neurovirulence level of the virus and were associated with ethical and economic difficulties in terms of broad application. Several strategies have been applied to develop mouse models of EV71 infection, including strategies that employ virus adaption and immunodeficient hosts. Although these mouse models do not closely mimic human disease, they have been applied to determine the pathogenesis of and treatment and prevention of the disease. EV71 receptor-transgenic mouse models have recently been developed and have significantly advanced our understanding of the biological features of the virus and the host-parasite interactions. Overall, each of these models has advantages and disadvantages, and these models are differentially suited for studies of EV71 pathogenesis and/or the pre-clinical testing of antiviral drugs and vaccines. In this paper, we review the characteristics, applications and limitation of these EV71 animal models, including non-human primate and mouse models.

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“…However their use raises several safety issues since pathogenic bioactive material can remain in vaccine formulations as contaminants (LPS, toxins …). Moreover, to maintain the efficacy of live pathogens, strict storage conditions must be adhered to in order to avoid instability and degradation, and a reversion or a reassortment of the attenuated pathogens with a wild-type, perhaps leading to the emergence of an infection-bearing vaccine, cannot be discounted [1].…”

Section: Introductionmentioning

confidence: 99%