Phase 3 Trial of a Sabin Strain–Based Inactivated Poliovirus Vaccine

Liao, Guoyang; Li, Rongcheng; Li, Changgui; Sun, Mingzhe; Jiang, Shimin; Li, Yanping; Mo, Zhaojun; Xia, Jielai; Xie, Zhihui; Che, Yanchun; Yang, Jingsi; Yin, Zhifang; Wang, Jianfeng; Chu, Junfeng; Cai, Wei; Zhou, Jian; Wang, Junzhi; Li, Qihan

doi:10.1093/infdis/jiw433

Cited by 29 publications

(19 citation statements)

References 20 publications

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“…12 While during 2012-2014, a phase Ⅲ trial of a Sabin IPV which was also conducted in Binyang and Pingle counties, Guangxi Province, China, reported similar level of maternal poliovirus antibody in infants with our study. 21 The differences in maternal antibody levels among these studies (including our study) might result from the regional disparity and the fluctuation of antibody level in different years. Our findings of the effect of high levels of maternal antibody on reduction of the serologic response to the Sabin and Salk IPVs were consistent with other investigations.…”

Section: Discussionmentioning

confidence: 61%

Effect of maternal antibody on the infant immune response to inactivated poliovirus vaccines made from Sabin strains

Tang

Cui

et al. 2019

Human Vaccines & Immunotherapeutics

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This study aimed to evaluate the effect of maternally derived antibody on the immunogenicity of Sabin IPV. A total of 600 infants were randomized to receive one of the five different vaccines: the high-(group A), medium-(group B) or low-dose (group C) of investigational Sabin IPV, the control Salk IPV (group D) or the control Sabin IPV (group E), at 2, 3 and 4 months of age. The post-vaccination GMTs, GMIs and seroconversion rates of poliovirus type-specific neutralizing antibody were analyzed for different maternal antibody levels. The correlations between maternal antibody levels and post-vaccination antibody responses were also modeled by linear regressions. The post-vaccination GMTs were significantly lower among infants with high maternal antibody titers for poliovirus type 1 or 2 mainly in the groups B, C, D and E. The GMIs and seroconversion rates decreased significantly with the increase of maternal antibody levels in all the five groups. In the groups A, B and C, maternal antibody levels were negatively associated with the postvaccination antibody titers (for poliovirus type 1 and 2) and the fold increases of post-vaccination antibody (for all the 3 poliovirus types). With the reduce of potency of the investigational Sabin IPVs, the linear regression coefficients increased accordingly in the groups A, B and C. In conclusion, high levels of maternal poliovirus antibody could attenuate the immune responses to the Sabin IPVs. Altering the potency of the investigational Sabin IPVs could alter the associations between maternal antibody levels and the serologic responses of infants.

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Section: Discussionmentioning

confidence: 61%

Effect of maternal antibody on the infant immune response to inactivated poliovirus vaccines made from Sabin strains

Tang

Cui

et al. 2019

Human Vaccines & Immunotherapeutics

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“…In parallel, increasing capacity has been targeted through the use of fractional intradermal 16 or adjuvanted 17 IPV doses. To date several Sabin-IPV (sIPV) have been assessed within clinical trials in adults 18,19 and infants, [20][21][22][23][24][25] and some are licensed in Japan 26 and China. 23 The IPV evaluated here is based on the safer-tomanufacture Sabin poliovirus strains and the PER.C6® platform.…”

Section: Introductionmentioning

confidence: 99%

“…To date several Sabin-IPV (sIPV) have been assessed within clinical trials in adults 18,19 and infants, [20][21][22][23][24][25] and some are licensed in Japan 26 and China. 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.…”

Section: Introductionmentioning

confidence: 99%

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

Leroux-Roels

Leroux‐Roels

Shukarev

et al. 2020

Human Vaccines & Immunotherapeutics

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This first-in-human study (NCT03032588), conducted in Belgium, evaluated a new inactivated poliovirus vaccines (IPV) candidate based on Sabin poliovirus strains grown on the high-yield PER.C6® cell line. Healthy adults (N = 32) were randomized (1:1) to receive a single dose of PER.C6-based Sabin-IPV (sIPV, 15:35:112.5 DU/dose) or conventional Salk-IPV (cIPV, 40:8:32 DU/dose). Reactogenicity was assessed up to 7 days after vaccination, immunogenicity 28 days after vaccination, and safety up to 6 months after vaccination. Solicited adverse events (AEs) were mild to moderate, no changes of concern in vital signs or safety laboratory values were observed, and no severe AEs (SAEs) or vaccine-related unsolicited AEs were reported after vaccination. A trend to more frequent solicited AEs after sIPV than after cIPV administration was observed. Most participants had preexisting neutralizing antibodies against poliovirus types (titer ≥8), which were strongly boosted by sIPV. Post-vaccination geometric mean titers were high (≥12,000) and similar across the two vaccination groups. Only participants with very high preexisting antibody levels did not show a vaccine-induced response, defined in seropositive participants as a 4-fold titer increase. The 10 initially seronegative (titer <8) participants (n = 5 in each study group) seroconverted and all participants had seroprotective antibody levels post-vaccination. The antibodies elicited by sIPV neutralized both Sabin and Salk poliovirus strains. In conclusion, the PER.C6®-based sIPV was well tolerated and highly immunogenic in adults with preexisting antibodies to poliovirus.

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“…However, previous investigations have shown that the Wistar rat model is not optimal for dose-finding studies of new sIPV vaccines, especially for type 2. Indeed, different immunogenicity profiles for poliovirus type 2 between Salk and Sabin based vaccine strains were observed in this rat model, while these vaccines showed comparable immunogenicity in Phase II and III clinical trials [7] , [11] , [12] , [25] , [26] . Consistent with these observations, we also observed lower immunogenicity and reduced potency of Sabin type 2 versus BRP2 in the Wistar rat model ( Fig.…”

Section: Discussionmentioning

confidence: 83%

“…In addition, the Institute of Medical Biology in Kunming, China, who brought the first stand-alone sIPV to the market in 2015, published an immunogenicity study in rhesus macaques showing that their DTaP-sIPV candidate vaccine induced neutralizing antibody titers that were similar to those generated by the control DTaP-cIPV and stand-alone sIPV [10] . Immunogenicity in humans was subsequently demonstrated in phase II and III clinical trials [11] , [12] , [13] .…”

Section: Introductionmentioning

confidence: 99%

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

Bockstal

Tiemessen

Achterberg

et al. 2018

Vaccine

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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.

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Phase 3 Trial of a Sabin Strain–Based Inactivated Poliovirus Vaccine

Abstract: The immune response induced by Sabin-IPV was not inferior to that established with Salk-IPV.

Cited by 29 publications

References 20 publications

Effect of maternal antibody on the infant immune response to inactivated poliovirus vaccines made from Sabin strains

Effect of maternal antibody on the infant immune response to inactivated poliovirus vaccines made from Sabin strains

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

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

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