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A phase Ⅱ, randomized, controlled trial to evaluate the safety and immunogenicity of a Sabin strain-based inactivated polio vaccine.

ABSTRACT: This phase Ⅱ, randomized, controlled trial aimed to evaluate the safety and immunogenicity of a various Sabin IPV preparations. Six hundred infants aged 60 ~ 90 days received one of five different vaccines: low- (group A), medium- (group B) or high-D antigen content (group C) of an experimental Sabin IPV, control Sabin IPV (group D) or control Salk IPV (group E), on a 0-1-2 month schedule. Participants were observed and followed up within 30 days of each dose to assess safety. Serum samples were collected before the first dose and 30 days after the third dose to assess immunogenicity. After three doses, type-1 seroconversion rates of groups A-E were 99.1%, 100.0%, 99.1%, 99.0%, and 93.4%, respectively; type-2 seroconversion rates were 93.5%, 97.1%, 98.1%, 95.1%, and 91.5%, respectively; and type-3 seroconversion rates were 95.4%, 98.1%, 98.1%, 95.1%, and 100.0%, respectively. Only type-1 seroconversion rates differed significantly for group E. The incidences of injection-site redness (A: 21.9%, B: 23.7%, C: 29.4%, D: 16.2%, E: 12.7%), swelling (A: 6.7%, B: 6.8%, C: 5.0%, D: 0.0%, E: 1.7%) and pain (A: 5.0%, B: 6.8%, C: 7.6%, D: 0.0%, E: 0.9%) all were significantly higher for experimental vaccines relative to control groups. No SAEs were detected related to vaccination, and most adverse reactions were mild or moderate in severity. In conclusion, the experimental Sabin IPVs with low-, medium-, and high-D antigen content all revealed good safety and immunogenicity profiles although being more reactogenic than the control vaccines.

SUBMITTER: Tang R

PROVIDER: S-EPMC7733909 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:A concerted action on the part of international agencies and national governments has resulted in the near-eradication of poliomyelitis. However, both the oral polio vaccine (OPV) and the inactivated polio vaccine (IPV) have deficiencies which make them suboptimal for use after global eradication. OPV is composed of attenuated Sabin strains and stimulates robust immunity, but may revert to neurovirulent forms in the intestine which can be shed and infect susceptible contacts. The majority of IPV products are manufactured using pathogenic strains inactivated with formalin. Upon eradication, the production of large quantities of pathogenic virus will present an increased biosecurity hazard. A logical ideal endgame vaccine would be an inactivated form of an attenuated strain that could afford protective immunity while safely producing larger numbers of doses per unit of virus stock than current vaccines. We report here the development of an ionizing radiation (IR)-inactivated Sabin-based vaccine using a reconstituted Mn-decapeptide (MDP) antioxidant complex derived from the radioresistant bacterium Deinococcus radiodurans. In bacteria, Mn2+-peptide antioxidants protect proteins from oxidative damage caused by extreme radiation exposure. Here we show for the first time, that MDP can protect immunogenic neutralizing epitopes in picornaviruses. MDP protects epitopes in Polio Virus 1 and 2 Sabin strains (PV1-S and PV2-S, respectively), but viral genomic RNA is not protected during supralethal irradiation. IR-inactivated Sabin viruses stimulated equivalent or improved neutralizing antibody responses in Wistar rats compared to the commercially used IPV products. Our approach reduces the biosecurity risk of the current PV vaccine production method by utilizing the Sabin strains instead of the wild type neurovirulent strains. Additionally, the IR-inactivation approach could provide a simpler, faster and less costly process for producing a more immunogenic IPV. Gamma-irradiation is a well-known method of virus inactivation and this vaccine approach could be adapted to any pathogen of interest.

Project description:The live-attenuated oral polio vaccine (OPV) will be no longer used when wild poliovirus (WPV) eliminating in worldwide, according to GPEI (the Global Polio Eradication Initiative) Reports. It is planning to replace OPV by Sabin-based inactivated poliovirus vaccine (sIPV) in developing countries, with purpose of reducing of the economic burden and maintaining of the appropriate antibody levels in population. It studied serial fractional doses immunized by intradermal injection (ID) in rats, to reduce consume of antigen and financial burden, maintaining sufficient immunogenicity; Methods: Study groups were divided in 4 groups of dose gradient, which were one-tenth (1/10), one-fifth (1/5), one-third (1/3) and one-full dose (1/1), according to the volume of distribution taken from the same batch of vaccine (sIPV). Wistar rats were injected intradermally with the needle and syringe sing the mantoux technique taken once month for 3 times. It was used as positive control that intramuscular inoculation (IM) was injected with one-full dose (1/1) with same batch of sIPV. PBS was used as negative control. Blood samples were collected via tail vein. After 30 d with 3 round of immunization, it analyzed the changes of neutralization antibody titers in the each group by each immunization program end; Results: The results of seroconversion had positive correlation with different doses in ID groups. The higher concentration of D-antigen (D-Ag) could conduct higher seroconversion. Furthermore, different types of viruses had different seroconversion trend. It showed that the geometric mean titers (GMTs) of each fractional-dose ID groups increased by higher concentration of D-Ag, and it got significant lower than the full-dose IM group. At 90th days of immunization, the GMTs for each poliovirus subtypes of fractional doses were almost higher than 1:8, implied that it could be meaning positive seroprotection titer for polio vaccine types, according to WHO suggestion; Conclusions: The fractional dose with one-fifth (1/5) could be used by intradermal injection to prevent poliovirus infection, if there were more human clinical detail research consistent with this findings in rats.

Project description:BackgroundIn a previous phase 3 clinical trial, we showed that an inactivated poliovirus vaccine derived from the Sabin strain (sIPV) can induce neutralising antibodies against currently circulating and reference wild poliovirus strains. However, the immune persistence of sIPV remains to be evaluated.MethodsIn this study, 400 participants who were eligible for an early phase 3 clinical trial (Jan 1, 2012-Aug 31, 2014) in Pingle County, GuanXi Province, China, were initially involved in one site. Of the participants in the previous phase 3 clinical trial, sera of 287, 262, 237, and 207 participants were sampled at the ages of 4, 6, 8, and 10 years, respectively, after the prime-boost regimen. Neutralising antibodies against attenuated Sabin strains were detected using these serum samples to determine immune persistence. The serum neutralising antibodies titre of 1:8 against poliovirus types 1, 2, and 3 is considered to be a seroprotection level for polio. The trial is registered at ClinicalTrials.gov, NCT01510366.FindingsThe protective rates against poliovirus types 1, 2, and 3 in the sIPV group were all 100% at 10 years after the booster immunisation, compared with 98.1%, 100%, and 97.1%, respectively, in the wIPV control group after 10 years. After the booster at 18 months, the geometric mean titres (GMTs) of neutralising antibodies against poliovirus types 1, 2, and 3 in the sIPV group were 13,265.6, 7856.7, and 6432.2, respectively, and the GMTs in the control group (inoculated with inactivated poliovirus vaccine derived from wild strain (wIPV)) were 3915.6, 2842.6, and 4982.7, respectively. With increasing time after booster immunisation, the GMTs of neutralising antibodies against poliovirus types 1, 2, and 3 gradually decreased in both the sIPV and wIPV groups. At the age of ten years, the GMTs of neutralising antibodies against poliovirus types 1, 2, and 3 in the sIPV group were 452.3, 392.8, and 347.5, respectively, and the GMTs in the wIPV group 108.5, 154.8, and 229.3, respectively, which were still at a higher-than-protective level (1:8).InterpretationBoth sIPV and wIPV maintained sufficiently high immune persistence against poliovirus types 1, 2, and 3 for at least 10 years after booster immunisation.FundingYunnan Provincial Science and Technology Department, the Bill and Melinda Gates Foundation, the National High-tech Research and Development Program, the National International Science and Technology Cooperation Project, the Yunnan Application Basic Research Project, the Innovation Team Project of Xie He, the Yunnan International Scientific and Technological Cooperation Project, and the Medical and Technology Innovation Project of Xie He.

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A phase Ⅱ, randomized, controlled trial to evaluate the safety and immunogenicity of a Sabin strain-based inactivated polio vaccine.

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