Immunogenicity and Safety of a Sabin Strain-Based Inactivated Polio Vaccine: A Phase 3 Clinical Trial.

BACKGROUND: The Sabin strain-based inactivated polio vaccine (sIPV) plays a vital role in eradicating poliomyelitis in developing countries. METHODS: The study was designed as a randomized, controlled, double-blinded, noninferiority trial. A total of 1200 healthy infants aged 60-90 days were enrolled and randomly assigned to receive 3 doses of either sIPV (the experimental arm) or IPV (the control arm) at days 0, 30, and 60. Immunogenicity and safety outcomes were assessed using the per-protocol and safety populations, respectively. RESULTS: A total of 553 and 562 participants in the sIPV and IPV groups, respectively, were included in the per-protocol population. Seroconversion rates in the sIPV and IPV groups were 98.0% and 94.1%, respectively, for type 1 poliovirus (P < .01); 94.8% and 84.0%, respectively, for type 2 (P < .01); and 98.9% and 97.7%, respectively, for type 3 (P = .11). A total of 599 and 600 participants in the sIPV and IPV groups, respectively, were included in the safety population. Fever was the most common adverse event, occurring in 61.6% and 49.8% of participants in the experimental and control arms, respectively (P < .01). CONCLUSIONS: The sIPV demonstrated an immunogenicity profile noninferior to that of the conventional IPV and had a good safety profile. CLINICAL TRIALS REGISTRATION: NCT03526978.

Evaluation of the use of various rat strains for immunogenic potency tests of Sabin-derived inactivated polio vaccines.

Slc:Wistar rats have been the only strain used in Japan for purpose of evaluating a national reference vaccine for the Sabin-derived inactivated polio vaccine (sIPV) and the immunogenicity of sIPV-containing products. However, following the discovery that the Slc:Wistar strain was genetically related to the Fischer 344 strain, other "real" Wistar strains, such as Crlj:WI, that are available worldwide were tested in terms of their usefulness in evaluating the immunogenicity of the past and current lots of a national reference vaccine. The response of the Crlj:WI rats against the serotype 1 of sIPV was comparable to that of the Slc:Wistar rats, while the Crlj:WI rats exhibited a higher level of response against the serotypes 2 and 3. The immunogenic potency units of a national reference vaccine determined using the Slc:Wistar rats were reproduced on tests using the Crlj:WI rats. These results indicate that a titer of the neutralizing antibody obtained in response to a given dose of sIPV cannot be directly compared between these two rat strains, but that, more importantly, the potency units are almost equivalent for the two rat strains.

Phase 3 Trial of a Sabin Strain-Based Inactivated Poliovirus Vaccine.

BACKGROUND: The development of a Sabin strain-based inactivated poliovirus vaccine (Sabin-IPV) is imperative to protecting against vaccine-associated paralytic poliomyelitis in developing countries. METHODS: In this double-blinded, parallel-group, noninferiority trial, eligible infants aged 60-90 days were randomly assigned in a ratio of 1:1 to receive either 3 doses of Sabin-IPV or Salk strain-based IPV (Salk-IPV) at 30-day intervals and a booster at the age of 18 months. Immunogenicity and safety were assessed on the basis of a protocol. RESULTS: Of 1438 infants, 1200 eligible infants were recruited and received either Sabin-IPV or Salk-IPV. From the Sabin-IPV and Salk-IPV groups, 570 and 564 infants, respectively, completed the primary immunization and formed the per-protocol population. The seroconversion rates of the participants who received Sabin-IPV were 100%, 94.9%, and 99.0% (types I, II, and III, respectively), and those of the participants who received Salk-IPV were 94.7%, 91.3%, and 97.9% 1 month after the completion of primary immunization. An anamnestic response for poliovirus types I, II, and III was elicited by a booster in both groups. Except in the case of fever, other adverse events were similar between the 2 groups. CONCLUSIONS: The immune response induced by Sabin-IPV was not inferior to that established with Salk-IPV.

Phase II and III Clinical Studies of Diphtheria-Tetanus-Acellular Pertussis Vaccine Containing Inactivated Polio Vaccine Derived from Sabin Strains (DTaP-sIPV).

BACKGROUND: Phase II and III clinical studies were conducted to evaluate immunogenicity and safety of a novel DTaP-IPV vaccine consisting of Sabin inactivated poliovirus vaccine (sIPV) and diphtheria-tetanus-acellular pertussis vaccine (DTaP). METHODS: A Phase II study was conducted in 104 healthy infants using Formulation H of the DTaP-sIPV vaccine containing high-dose sIPV (3, 100, and 100 D-antigen units for types 1, 2, and 3, respectively), and Formulations M and L, containing half and one-fourth of the sIPV in Formulation H, respectively. Each formulation was administered 3 times for primary immunization and once for booster immunization. A Phase III study was conducted in 342 healthy infants who received either Formulation M + oral polio vaccine (OPV) placebo or DTaP + OPV. The OPV or OPV placebo was orally administered twice between primary and booster immunizations. RESULTS: Formulation M was selected as the optimum dose. In the Phase III study, the seropositive rate was 100% for all Sabin strains after primary immunization, and the neutralizing antibody titer after booster immunization was higher than in the control group (DTaP + OPV). All adverse reactions were clinically acceptable. CONCLUSIONS: DTaP-sIPV was shown to be a safe and immunogenic vaccine. CLINICAL TRIALS REGISTRATION: JapicCTI-121902 for Phase II study, JapicCTI-101075 for Phase III study (http://www.clinicaltrials.jp/user/cte_main.jsp).

Immune Persistence following Primary Immunization and the Immunogenicity and Safety of a Booster Dose of a Multidose Sabin Strain-Based Inactivated Polio Vaccine in Infants Aged 18 Months.

BACKGROUND: The multidose Sabin-strain inactivated poliovirus vaccine (sIPV) has the potential to significantly aid in the eradication of poliomyelitis, particularly in low- and middle-income countries. As part of a phase III clinical trial in which infants were given three doses of primary immunization at 2, 3, and 4 months of age, this study aimed to evaluate immune persistence following primary immunization, as well as the safety and immunogenicity of a booster of the 5-dose sIPV in infants aged 18 months. METHODS: Infants aged 18 months were given one booster dose of 5-dose sIPV in stage one, which was open-label. Unblinding was performed for stage two after completing primary immunization, which was randomized, blinded, and controlled; infants aged 18 months in the test group I-III, IPV group, and single-dose sIPV group were given one booster dose of 5-dose sIPV, conventional IPV, and single-dose sIPV, respectively, in stage two. RESULTS: This study included 1438 infants in the immune persistence and safety set and 1387 infants in the booster per-protocol set. Fourteen months after primary immunization, the seropositivity rates (≥1:8) for types 1-3 were 100%, 99.88%, and 99.53% in the 5-dose sIPV groups; 100%, 98.97%, and 97.23% in the IPV group; and 99.66%, 100%, and 99.66% in the single-dose sIPV group. A total of 30 days after booster immunization, the seropositivity rates (≥1:8) of 3 serotypes in all the groups reached 100%. The geometric mean titers of neutralizing antibodies for types 1-3 in the 5-dose sIPV group were 9962.89, 10273, and 7870.21, with geometric mean increases of 15.76, 33.15, and 24.5, compared to the pre-booster level. The overall incidence of adverse reactions was 8.97%, with fever being the most common, observed at rates of 7.1%, 5.52%, and 7.96% in the 5-dose sIPV, IPV, and single-dose groups, respectively (p = 0.4845). CONCLUSIONS: The 5-dose sIPV has shown promising immune persistence and robust immune response following a booster immunization, coupled with an acceptable safety profile.

Immunogenicity and lot-to-lot consistency of booster shot with Sabin inactivated poliomyelitis vaccine in Chinese children aged 18-24 Months: A phase â £ clinical trial.

BACKGROUND: There has been no data on the immunogenicity and safety of the 4th booster dose of the sIPV immunization in 18-24 months old children in post-marketing studies of large cohort providing with robust results. METHOD: In a phase Ⅳ randomized, double-blinded clinical trial, 1200 participants aged 2 months were immunized with three consecutive doses of sIPV at 2, 3, and 4 months old to complete primary immunization. Out of the 1200 participants, 1129 received the 4th dose of sIPV as booster immunization. Immunogenicity was evaluated in 1100 participants. RESULTS: Seropositive rates of the anti-poliovirus type 1, 2, and 3 neutralizing antibodies were 99.9 %, 98.0 %, 98.2 %, respectively, with GMTs of 557.0, 146.1, 362.0 one year after primary vaccination. After booster vaccination between 18 and 24 months old, the seropositive rates for 3 types all reached 100.0 %, with GMTs of 8343.6, 5039.6, 5492.0, respectively. Particularly for the anti-poliovirus type 2 antibody, the GMT was 230.4 after primary immunization, maintained to 146.1 one year after primary immunization, and increased to as high as 5039.6 after booster vaccination. The GMT ratios between each batch groups after booster immunization were between 0.67 and 1.50, meeting the immunological equivalence criteria. The incidence rate of adverse reaction was 23.0 %, which was comparable to those in the phase Ⅲ trial but had a lower incidence. Furthermore, no SUSAR was reported in this study. INTERPRETATION: In conclusion, as the anti-poliovirus antibodies gradually waned one year post sIPV primary vaccination, especially the type 2 antibody waned to a very low level, suggesting the importance of the booster immunization for children at the age of 18-24 months old. The booster shot can greatly enhance the antibody level and protect children from the potential risk of infection with WPV and VDPV by supplementing the anti-poliovirus type 2 immunity gap in the current real world. Clinic Trial Registration. NCT04224519.

Quantitative Analysis of the Instant and Persistent Inhibition Effects of Maternal Poliovirus Antibodies on the Immune Response in a Phase IV Trial of a Sabin Strain-Based Inactivated Poliovirus Vaccine.

BACKGROUND: An inactivated poliomyelitis vaccine made from Sabin strains (sIPVs) has widely been used in China since 2015. However, the quantitative data on the instant and persistent inhibition effects of maternal poliovirus antibodies on the immune response to sIPV priming and booster vaccination have not been available yet. OBJECTIVE: In this study, we aim to explore and quantify the instant and persistent inhibition effect of maternal poliovirus antibodies on the immune response elicited by sIPV primary and booster vaccination. METHODS: The immunogenicity data consisting of the days 0 and 30 after the prime and booster vaccination of the sIPV in a phase IV trial were pooled for a quantitative analysis of the inhibition effect of maternal poliovirus antibody. The geometric mean ratio (GMR) was calculated using linear regression models, representing that every 2-fold higher maternal poliovirus antibody titer may result in a (1-GMR) lower postimmunization antibody titer. RESULTS: The GMRs for poliovirus types 1, 2, and 3 were 0.79 (0.77-0.82), 0.85 (0.81-0.89), and 0.87 (0.83-0.91) at 30 days after the priming series, 0.86 (0.83-0.89), 0.81 (0.76-0.85), and 0.86 (0.80-0.93) at one year after the priming series, and 0.96 (0.94-0.99), 0.89 (0.86-0.93), and 0.98 (0.93-1.03) at 30 days after the booster dose. The inhibition effect continued to exist until the booster dose 1 year later, and such a persistent inhibition effect was almost attenuated for poliovirus types 1 and 3, and partly reduced for type 2 at 30 days after the booster dose. CONCLUSION: A wider interval between the four sIPV doses might be a consideration for reducing the effect of maternal antibodies and subsequently eliciting and maintaining higher antibody levels to protect against poliovirus transmission and infection at the final stage of polio eradication in the global world. This study's clinical trial registry number is NCT04224519.

Modeling the spread of circulating vaccine-derived poliovirus type 2 outbreaks and interventions: A case study of Nigeria.

Background: Despite the successes of the Global Polio Eradication Initiative, substantial challenges remain in eradicating the poliovirus. The Sabin-strain (live-attenuated) virus in oral poliovirus vaccine (OPV) can revert to circulating vaccine-derived poliovirus (cVDPV) in under-vaccinated communities, regain neurovirulence and transmissibility, and cause paralysis outbreaks. Since the cessation of type 2-containing OPV (OPV2) in 2016, there have been cVDPV type 2 (cVDPV2) outbreaks in four out of six geographical World Health Organization regions, making these outbreaks a significant public health threat. Preparing for and responding to cVDPV2 outbreaks requires an updated understanding of how different factors, such as outbreak responses with the novel type of OPV2 (nOPV2) and the existence of under-vaccinated areas, affect the disease spread. Methods: We built a differential-equation-based model to simulate the transmission of cVDPV2 following reversion of the Sabin-strain virus in prolonged circulation. The model incorporates vaccinations by essential (routine) immunization and supplementary immunization activities (SIAs), the immunity induced by different poliovirus vaccines, and the reversion process from Sabin-strain virus to cVDPV. The model's outcomes include weekly cVDPV2 paralytic case counts and the die-out date when cVDPV2 transmission stops. In a case study of Northwest and Northeast Nigeria, we fit the model to data on the weekly cVDPV2 case counts with onset in 2018-2021. We then used the model to test the impact of different outbreak response scenarios during a prediction period of 2022-2023. The response scenarios included no response, the planned response (based on Nigeria's SIA calendar), and a set of hypothetical responses that vary in the dates at which SIAs started. The planned response scenario included two rounds of SIAs that covered almost all areas of Northwest and Northeast Nigeria except some under-vaccinated areas (e.g., Sokoto). The hypothetical response scenarios involved two, three, and four rounds of SIAs that covered the whole Northwest and Northeast Nigeria. All SIAs in tested outbreak response scenarios used nOPV2. We compared the outcomes of tested outbreak response scenarios in the prediction period. Results: Modeled cVDPV2 weekly case counts aligned spatiotemporally with the data. The prediction results indicated that implementing the planned response reduced total case counts by 79% compared to no response, but did not stop the transmission, especially in under-vaccinated areas. Implementing the hypothetical response scenarios involving two rounds of nOPV2 SIAs that covered all areas further reduced cVDPV2 case counts in under-vaccinated areas by 91-95% compared to the planned response, with greater impact from completing the two rounds at an earlier time, but it did not stop the transmission. When the first two rounds were completed in early April 2022, implementing two additional rounds stopped the transmission in late January 2023. When the first two rounds were completed six weeks earlier (i.e., in late February 2022), implementing one (two) additional round stopped the transmission in early February 2023 (late November 2022). The die out was always achieved last in the under-vaccinated areas of Northwest and Northeast Nigeria. Conclusions: A differential-equation-based model of poliovirus transmission was developed and validated in a case study of Northwest and Northeast Nigeria. The results highlighted (i) the effectiveness of nOPV2 in reducing outbreak case counts; (ii) the need for more rounds of outbreak response SIAs that covered all of Northwest and Northeast Nigeria in 2022 to stop the cVDPV2 outbreaks; (iii) that persistent transmission in under-vaccinated areas delayed the progress towards stopping outbreaks; and (iv) that a quicker outbreak response would avert more paralytic cases and require fewer SIA rounds to stop the outbreaks.

Immuno-persistence of the different primary polio vaccine schedules and immunogenicity of the booster dose by sabin inactivated or bivalent oral poliovirus vaccine in children aged 4 years: an open-label, randomised, controlled phase 4 trial in China.

Background: Sabin inactivated and bivalent oral poliovirus vaccine (sIPV, bOPV) were commonly used in China since 2016. We conducted an open-label, randomised, controlled phase 4 trial to assess immune persistence following sequential immunisation with sIPV or bOPV, and immunogenicity and safety of a booster dose of poliovirus vaccine in children aged 4 years. Methods: Participants from a previous clinical trial with three different sequential schedules with sIPV (I) or bOPV (B) at ages 2, 3, and 4 months (Groups I-B-B, I-I-B, I-I-I) in 2017 were followed-up. The children were further divided into five subgroups after sIPV was given for Group I-B-B, and sIPV or bOPV randomly given for Group I-I-B and Group I-I-I (128 children in Groups I-B-B-I, 60 in Group I-I-B-B, 64 in Group I-I-B-I, 68 in Group I-I-I-B, 67 in Group I-I-I-I). Immune persistence and immunogenicity were assessed by measuring poliovirus type-specific antibodies, and safety were analysed in all children who received the booster dose. Findings: Between Dec 5, 2020 and Jun 30, 2021, we respectively enrolled 381 participants in the immune persistence analysis, and 352 participants in per protocol (PP) analysis of the immunogenicity of the booster immunisation. Seropositivity rates of antibodies against poliovirus types 1 and 3 were all >90% four years after primary immunisation, while for poliovirus type 2 were 46.83%, 75.41%, and 90.23% (χ2 = 60.948, P < 0.001) for Groups I-B-B, I-I-B, and I-I-I, respectively. After the booster dose, seropositivity rates were 100% for all three serotypes in Group I-B-B-I, I-I-B-I and I-I-I-I; In Group I-I-B-B and I-I-I-B, the seropositivity rates for types 1 and 3 were all 100%, for type 2 were 92.59% and 98.46%. The geometric mean titres (GMTs) against poliovirus 1 and 3 were all high in five groups (>1860.73), and the GMTs against type 2 were significantly lower in groups booster with bOPV: Group I-I-B-B (50.60) and Group I-I-I-B (247.84). There was no significant difference in seropositivity rates or GMTs for all three serotypes (P > 0.05) between Group I-I-B-I and I-I-I-I. No serious adverse events occurred during the study. Interpretation: Our findings suggest that at least two sIPV doses are needed in the current routine poliovirus immunisation schedule, and schedules containing 3 or 4 doses of sIPV provide better protection against poliovirus type 2 than the current sIPV-sIPV-bOPV-bOPV schedule in China. Funding: Medical and Health Science and Technology of Zhejiang Province (2021KY118). This trial was registered with ClinicalTrials.gov (NCT04576910).

Immunogenicity and immune persistence in 4-year-old children completing four doses of Sabin strain or wild strain inactivated poliovirus vaccine: A phase IV, open-labeled, parallel-controlled observational study.

BACKGROUND: Sabin strain inactivated poliovirus vaccine (hereinafter as "sIPV") has been marketed globally in recent years, and more data on its immune persistence are needed. METHODS: This is a phase IV, open-labeled, parallel-controlled observational study based on phase III clinical trial as required by the China National Medical Products Administration (NMPA). At least 450 subjects aged four years (48-54 months) who received four doses at 2, 3, 4 and 18 months of age of sIPV or wild strain poliovirus vaccine (wIPV) in phase III clinical trial enrolled at a 2:1 ratio and collected blood samples for neutralizing antibody testing. RESULTS: A total of 500 subjects of four years old (334 in the sIPV group and 166 in wIPV group) were finally enrolled. The seropositivity rates (≥1:8) of neutralizing antibodies against serotype I-III were all 100.00% in all participants, and the geometric mean titers (GMT) were 1117.33 vs. 337.77 against serotype I, 632.72 vs. 267.34 against serotype Ⅱ, 1665.98 vs. 923.02 against serotype III in the sIPV group and wIPV group respectively at 4 years old. The seropositivity rates and GMTs of neutralizing antibodies in the test group were non-inferior to that of the control group against all three serotypes at different time points (P < 0.0001). The antibody GMT experienced a 10-fold, 8-fold, and 7-fold decline for serotypes I, Ⅱ, and III in the sIPV group, and a 13-fold, 7-fold, and 7-fold decline in the wIPV group from one month after booster vaccination to 4 years old. CONCLUSIONS: The neutralizing antibody level is much higher than the seroprotection cutoff (≥1:8) among children of 4 years old who completed the four-dose vaccination of either sIPV or wIPV. Therefore, another booster vaccination is not recommended at 4 years old. Longer immune persistence observation is still ongoing. REGISTRATION: ClinicalTrials.gov Identifier: NCT04989231.

Safety, immunogenicity, and lot-to-lot consistency of a multidose Sabin strain-based inactivated polio vaccine: a phase III, randomized, blinded, positive-control clinical trial in infants aged 2 months.

OBJECTIVES: To evaluate the safety, immunogenicity, and lot-to-lot consistency of Sabin strain-based inactivated polio vaccine (sIPV) in a five-dose vial presentation. METHODS: Stage I was an open-label safety observation, in which 72 healthy subjects (including 24 adults, children, and infants each) were given one or three doses of the five-dose vial sIPV; stage II was a randomized, blinded, and positive-control study, in which 1500 infants were randomized at the ratio of 1: 1: 1: 1: 1 into five groups to receive either three doses of the five-dose sIPV three lots, a conventional inactivated poliovirus vaccine, or a single-dose sIPV as controls, for primary immunization. Safety, immunogenicity, and lot-to-lot consistency were assessed. RESULTS: Among 1456 subjects who completed the primary immunization, the geometric mean titer ratios of types 1, 2, and 3 of each pair of lots were all within the equivalence criteria margin (0.67-1.50). The seroconversion rates of types 1, 2, and 3 in the combined test group were 98.02%, 94.07%, and 98.77%, respectively, which were noninferior to both control groups. The overall incidence of adverse reactions was 29.68% and erythema was the most common adverse reaction with incidences of 10.47%,9.33%, and 9.73% in the combined test group and control groups (P >0.05). CONCLUSION: The five-dose sIPV demonstrated good safety, immunogenicity, and lot-to-lot consistency.

Immune persistence of an inactivated poliovirus vaccine derived from the Sabin strain: a 10-year follow-up of a phase 3 study.

Background: In 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. Methods: In 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. Findings: The 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). Interpretation: Both sIPV and wIPV maintained sufficiently high immune persistence against poliovirus types 1, 2, and 3 for at least 10 years after booster immunisation. Funding: Yunnan 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.

Cost-effectiveness of various immunization schedules with inactivated Sabin strain polio vaccine in Hangzhou, China.

Background: It is necessary to select suitable inactivated poliovirus vaccine(IPV) and live, attenuated oral poliovirus vaccine (OPV) sequential immunization programs and configure the corresponding health resources. An economic evaluation was conducted on the sequential procedures of Sabin strain-based IPV (sIPV) and bivalent OPV (bOPV) with different doses to verify whether a cost-effectiveness target can be achieved. This study aimed to evaluate the cost-effectiveness of different sIPV immunization schedules, which would provide convincing evidence to further change the poliovirus vaccine (PV) immunization strategies in China. Methods: Five strategies were included in this analysis. Based on Strategy 0(S0), the incremental cost (IC), incremental effect (IE), and incremental cost-effectiveness ratio (ICER) of the four different strategies (S1/S2/S3/S4) were calculated based on the perspective of the society. Seven cost items were included in this study. Results of field investigations and expert consultations were used to calculate these costs. Results: The ICs of S1/S2/S3/S4 was Chinese Yuan (CNY) 30.77, 68.58, 103.82, and 219.82 million, respectively. The IE of vaccine-associated paralytic poliomyelitis (IEVAPP) cases of S1/S2/S3/S4 were 0.22, 0.22, 0.22, and 0.11, respectively, while the IE of disability-adjusted life-years (IEDALY) of S1/S2/S3/S4 were 8.98, 8.98, 8.98, and 4.49, respectively. The ICERVAPP of S1/S2/S3/S4 gradually increased to CNY 13.99, 31.17, 47.19, and 199.83 million/VAPP, respectively. The ICERDALY of S1/S2/S3/S4 also gradually increased to CNY 0.34, 0.76, 1.16, and 4.90 million/DALY, respectively. Conclusion: ICERVAPP and ICERDALY were substantially higher for S3 (four-sIPV) and S4 (replacement of self-funded sIPV based on one-sIPV-three-bOPV). Two-sIPV-two-bOPV had a cost-effectiveness advantage, whereas S2/S3/S4 had no cost-effectiveness advantage.

Safety, Immunogenicity and Lot-to-Lot Consistency of Sabin-Strain Inactivated Poliovirus Vaccine in 2-Month-Old Infants: A Double-Blind, Randomized Phase III Trial.

BACKGROUND: The Sabin-strain-based inactivated poliovirus vaccine (sIPV) plays an important role in poliomyelitis eradication in developing countries. As part of the phase III clinical development program, this study aimed to evaluate the safety, immunogenicity and lot-to-lot consistency of the sIPV in 2-month-old infants. METHOD: We conducted a phase III, randomized, double-blind, positive-controlled trial in which 1300 healthy infants were randomly assigned to four groups in a 1:1:1:1 ratio to receive one of the three lots of the sIPV or the control IPV at 2, 3 and 4 months of age. Serum samples were collected before the first dose and 30 days after the third dose of vaccination to assess the immunogenicity. Solicited local and systemic reactions were recorded within 7 days and unsolicited adverse events within 30 days after each vaccination. RESULTS: Of the 1300 randomized infants, 1190 infants completed the study and were included in the per-protocol population. The seroconversion rates in the three lots of the sIPV were 95.67%, 97.03% and 95.59%, respectively, for type 1; 94.33%, 93.73% and 92.88%, respectively, for type 2; and 98.67%, 99.67% and 99.32%, respectively, for type 3. The ratios of GMTs for poliovirus types 1, 2 and 3 of each pair of lots were all between 0.67 and 1.50, therefore meeting the predefined immunological equivalence criteria. For the seroconversion rate of poliovirus types 1, 2 and 3, the pooled sIPV group was non-inferior to the IPV group. The incidence of solicited and unsolicited adverse reactions (ARs) was similar in the pooled sIPV lots and the IPV group, and most of them were mild to moderate in severity. Non-vaccine-related serious adverse events (SAEs) were reported. CONCLUSIONS: Three consecutive lots of sIPV demonstrated robust and consistent immunogenicity. The safety and tolerability of the sIPV was acceptable and similar to that of the IPV.

Safety evaluation on concomitant immunization with inactivated poliomyelitis vaccine produced from Sabin strains and other vaccines (from 2015 to 2020).

OBJECTIVE: To evaluate the safety of concomitantly administering inactivated poliomyelitis vaccine produced from Sabin strains (sIPVs) with other vaccines. METHODS: A descriptive analysis was carried out on adverse events following immunization (AEFI) based on the administration of sIPV alone or concomitant with other vaccines (from 2015 to 2020) using data from the national AEFI surveillance system of China (CNAEFIS). All adverse reactions (ADRs) of the concomitant immunization were coded using a medical dictionary for regulatory activities (MedDRA) before comparison. RESULTS: The CNAEFIS reported a total of 9130 sIPV-related AEFI cases, including 6842 AEFI cases collected after immunization with sIPV alone and 2288 AEFI cases collected after immunization of sIPV concomitant with other vaccines. The combination of sIPV with diphtheria, tetanus and pertussis vaccine (DTaP) was correlated with the highest frequency of AEFI, which accounted for 53.50% of all 2288 AEFI cases. After MedDRA-based coding, the most frequent ADR was fever (70.18%), followed by erythema and swelling at the injection site (6.95%), induration at the injection site (3.85%), dermatitis allergy (3.56%) and urticaria (1.55%). A statistically significant difference (P < .001) was found between sIPV immunization and sIPV immunization concomitant with other vaccines for general reactions (95.36% and 93.22%, respectively) and abnormal reactions (4.64% and 6.78%, respectively). CONCLUSION: No new safety signal is found for sIPV administered concomitantly, although its administration with other vaccines may increase the occurrence of abnormal reactions. Vaccine manufacturers should focus on the safety of administering sIPV with DTaP and carry out relevant clinical studies when necessary.

Immunogenicity of two-dose and three-dose vaccination schedules with Sabin inactivated poliovirus vaccine in China: An open-label, randomized, controlled trial.

BACKGROUND: We assessed immunogenicity of three-dose and two-dose immunization schedules with a Sabin-strain inactivated poliovirus vaccine (sIPV) produced by one Chinese vaccine manufacturer. METHODS: This was an open label, randomized, controlled trial conducted in 16 vaccination clinics in Shandong province. Infants were allocated randomly to either a 3-dose study arm (sIPV administered at 2, 3, and 4 months of age) or a 2-dose arm (sIPV administered at 4 and 8-11 months of age). Poliovirus neutralizing antibodies were measured in sera collected prior to the first sIPV dose and one month after the last dose. FINDINGS: We enrolled 560 infants; 536 (95.7%) completed the study. Final seropositivity rates were >98% for all three serotypes in both study arms. There were no statistically significant differences in seropositivity between the 2-dose and the 3-dose schedule. Final median reciprocal titres of polio antibodies were high overall (>1:768 for all serotypes) and statistically significantly higher in 2-dose recipients compared with 3-dose recipients (p < 0.001). INTERPRETATION: This study offers evidence that two doses of sIPV administered at 4 and 8-11 months of age and three doses of sIPV administered at 2, 3, and 4 months of age both provide serological protection against poliomyelitis. Median reciprocal titres of polio antibodies were high overall, and were more related to the interval between doses than the number of doses, with the longer interval of the 2-dose schedule producing higher reciprocal titres than the shorter-interval 3-dose schedule. The protection provided by the 3-dose schedule is achieved earlier in life than the protection with the 2-dose schedule. Countries planning to use an IPV-only schedule in the post-eradication era can consider this 2-dose sIPV option as an immunogenic and dose-sparing strategy. FUNDING: World Health Organization (from a grant from International PolioPlus Committee, Rotary International, Evanston, IL, USA).

Immunogenicity and Safety of Inactivated Sabin-Strain Polio Vaccine "PoliovacSin": Clinical Trials Phase I and II.

Global polio eradication requires both safe and effective vaccines, and safe production processes. Sabin oral poliomyelitis vaccine (OPV) strains can evolve to virulent viruses and result in poliomyelitis outbreaks, and conventional inactivated poliomyelitis vaccine (Salk-IPV) production includes accumulation of large stocks of neurovirulent wild polioviruses. Therefore, IPV based on attenuated OPV strains seems a viable option. To increase the global supply of affordable inactivated vaccine in the still not-polio free world we developed an IPV made from the Sabin strains-PoliovacSin. Clinical trials included participants 18-60 years of age. A phase I single-center, randomized, double-blind placebo-controlled clinical trial included 60 participants, who received one dose of PoliovacSin or Placebo. A phase II multicenter, randomized, double-blind, comparative clinical trial included 200 participants, who received one dose of PoliovacSin or Imovax Polio. All vaccinations were well tolerated, and PoliovacSin had a comparable safety profile to the Placebo or the reference Imovax Polio preparations. A significant increase in neutralizing antibody levels to polioviruses types 1-3 (Sabin and wild) was observed in PoliovacSin and Imovax Polio vaccinated groups. Therefore, clinical trials confirmed good tolerability, low reactogenicity, and high safety profile of the PoliovacSin and its pronounced immunogenic properties. The preparation was approved for clinical trials involving infants.

Cross-neutralization Capacity of Immune Serum from Different Dosage of Sabin Inactivated Poliovirus Vaccine Immunization against Multiple Individual Polioviruses.

Introduction: Sabin strain inactivated poliovirus vaccine (sIPV) developed by Sinovac Biotech Co., Ltd., has shown good safety and immunogenicity against parental strains among infants in several finished pre-licensure clinical trials.Areas covered: To further study the neutralizing capacity of investigational sIPV immune serum against Sabin, Salk and recently circulating poliovirus strains, neutralization assay against ten individual strains was performed on backup serum collected from 250 infant participants of the finished phase II clinical trial.Expert commentary:: The sIPV can generate good immunogenicity against Sabin, Salk and recently circulating poliovirus strains. Taking into account its lower containment requirements and financial costs compared with the conventional Salk strain inactivated poliovirus vaccine, sIPV is an affordable and practical option for polio eradication.

Immunogenicity and safety of sabin-strain based inactivated poliovirus vaccine replacing salk-strain based inactivated poliovirus vaccine: An innovative application of different strain-IPVs replacement.

BACKGROUND: A domestic Sabin strain-based inactivated poliovirus vaccine (Sabin IPV) was approved by China Food and Drug Administration in 2017 as a replacement for the Salk strain-based inactivated poliovirus vaccine (Salk IPV) that has been in use in China for over 10 years. The present post-marketing trial was implemented in China to assess the immunogenicity and safety of replacing the Salk IPV with the Sabin IPV in the last two immunizations of the standard three-dose schedule. METHODS: We conducted a randomized, controlled clinical trial with two groups that received three doses of IPVs at the age of 2, 3, and 4 months: the Salk-Sabin-Sabin group and the Salk-Salk-Salk group. Blood samples were collected before vaccination and 30-40 days after the third dose of vaccination. The seroconversion rates and antibody geometric mean titers (GMTs) were calculated and analyzed to evaluate immunogenicity. The safety of both immunization schedules was also monitored and analyzed. RESULTS: Of 360 recruited healthy infants, all three IPV doses were administered and blood collection was completed in 330 infants. All participants (100%) in both groups were seropositive for all three poliovirus types after the last vaccination. There were significant differences between the two groups (P < 0.001) in the GMTs for antibodies against poliovirus types 1 and 2, but no significant difference was observed for antibodies against type 3 (P = 0.009). A non-inferiority t-test showed that the post-immunization GMTs for all three types in the Salk-Sabin-Sabin group were not inferior to those in the Salk-Salk-Salk group (P < 0.001). Safety assessment indicated that there was no significant difference in the incidence of all adverse events between the two groups (P = 0.806). CONCLUSIONS: The Salk-Sabin-Sabin IPV immunization schedule is not inferior to the Salk-Salk-Salk IPV schedule in terms of both immunogenicity and safety. Clinical trial number: NCT04051736.