Dataset Information

Genetically Thermo-Stabilised, Immunogenic Poliovirus Empty Capsids; a Strategy for Non-replicating Vaccines.

ABSTRACT: While wild type polio has been nearly eradicated there will be a need to continue immunisation programmes for some time because of the possibility of re-emergence and the existence of long term excreters of poliovirus. All vaccines in current use depend on growth of virus and most of the non-replicating (inactivated) vaccines involve wild type viruses known to cause poliomyelitis. The attenuated vaccine strains involved in the eradication programme have been used to develop new inactivated vaccines as production is thought safer. However it is known that the Sabin vaccine strains are genetically unstable and can revert to a virulent transmissible form. A possible solution to the need for virus growth would be to generate empty viral capsids by recombinant technology, but hitherto such particles are so unstable as to be unusable. We report here the genetic manipulation of the virus to generate stable empty capsids for all three serotypes. The particles are shown to be extremely stable and to generate high levels of protective antibodies in animal models.

SUBMITTER: Fox H

PROVIDER: S-EPMC5245777 | biostudies-other | 2017 Jan

REPOSITORIES: biostudies-other

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Genetically Thermo-Stabilised, Immunogenic Poliovirus Empty Capsids; a Strategy for Non-replicating Vaccines.

Fox Helen H Knowlson Sarah S Minor Philip D PD Macadam Andrew J AJ

PLoS pathogens 20170119 1

While wild type polio has been nearly eradicated there will be a need to continue immunisation programmes for some time because of the possibility of re-emergence and the existence of long term excreters of poliovirus. All vaccines in current use depend on growth of virus and most of the non-replicating (inactivated) vaccines involve wild type viruses known to cause poliomyelitis. The attenuated vaccine strains involved in the eradication programme have been used to develop new inactivated vacci ...[more]

PMID: 28103317

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Project description:BACKGROUND:Maternal poliovirus antibodies could provide passive immunity to the newborns from poliovirus infection during their first few months of life, but they may impair the immune responses of infants to the poliovirus vaccine as well. In our study, we pooled the data from three clinical trials of the inactivated poliovirus vaccine (IPV) based on Sabin strains to investigate the effect of maternal poliovirus antibodies on the immune responses of infants to poliovirus vaccines. METHODS:There were five groups in the pooled analysis, including low-dose Sabin IPV, medium-dose Sabin IPV, high-dose Sabin IPV, control Sabin IPV, and control Salk IPV groups. We reclassified the infants in different groups according to their maternal poliovirus antibodies by two methods, the first one included maternal antibody negative (<?1:8) and maternal antibody positive (?1:8), and the second one included maternal antibody titer <?1:8, 1:8?~?<?1:32 and???1:32. Then, we compared the geometric mean titers (GMTs), geometric mean antibody fold increases (GMIs) and seroconversion rates of poliovirus type-specific neutralizing antibodies after vaccination among participants with different maternal poliovirus antibody levels. RESULTS:The GMTs and GMIs of three types of poliovirus antibodies after vaccination in maternal antibody negative participants were significantly higher than those in maternal antibody positive participants. The seroconversion rates of type II and type III poliovirus antibodies in maternal antibody positive participants were significantly lower than those in maternal antibody negative participants. Among participants with maternal antibody titer <?1:8, 1:8?~?<?1:32 and???1:32, the GMTs and GMIs of three types of poliovirus antibodies after vaccination showed a tendency to decline with the increasing of maternal antibody levels. The seroconversion rates of three types of poliovirus antibodies in participants with maternal antibody titer ?1:32 were significantly lower than those in participants with maternal antibody titer <?1:8 and 1:8?~?<?1:32. CONCLUSIONS:Maternal poliovirus antibodies interfered with the immune responses of infants to poliovirus vaccines, and a high level of maternal antibodies exhibited a greater dampening effect. TRIAL REGISTRATION:ClinicalTrials.gov NCT04264598 February 11, 2020; ClinicalTrials.gov NCT04264546 February 11, 2020; ClinicalTrials.gov NCT03902054 April 3, 2019. Retrospectively registered.

Dataset Information

Genetically Thermo-Stabilised, Immunogenic Poliovirus Empty Capsids; a Strategy for Non-replicating Vaccines.

Publications

Genetically Thermo-Stabilised, Immunogenic Poliovirus Empty Capsids; a Strategy for Non-replicating Vaccines.

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