Immunogenicity and Safety of the Booster Dose of Polio Vaccine With Different Primary Sequential Schedules in China

Study Overview
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Brief Summary
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This study is to evaluate the immunogenicity and safety of Sabin IPV or bOPV, given as a booster vaccination in children aged 4 years who were previously immunised with different sequential immunization history by Sabin IPV and bOPV, and to observe the antibody persistence three years after different primary sequential immunization with Sabin IPV or bOPV at age 2, 3 and 4 months.

Detailed Description
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This is a continuous study of preliminary trial (Immunogenicity of three sequential schedules with Sabin inactivated poliovirus vaccine and bivalent oral poliovirus vaccine in Zhejiang, China: NCT03147560) . The investigators will follow up previous participants at age 4 years old with different primary sequential immunization schedules at age 2, 3 and 4 months: sIPV-bOPV-bOPV , sIPV-sIPV-bOPV , or sIPV-sIPV-sIPV, and give the 4th doses of polio vaccine with Sabin IPV or bOPV. A pre-vaccination blood sample is taken for polio antibody determinations. Sabin IPV will be administrated for participants in the previous Group 1 (sIPV-bOPV-bOPV), and Sabin IPV or bOPV will be given for participants in the previous Group 2 (sIPV-sIPV-bOPV) and Group 3 (sIPV-sIPV-sIPV) after they were randomly divided into two subgroups. At least two active surveillance visits, during which staff visited the participants s at home (on days 3 and 30) will required after vaccination to collect adverse reaction data. Parents or legal guardians were instructed to contact investigators if they observed any possible vaccine-related adverse events or important medical events (such as serious illness, physical disability, or death). The second blood sample will be collected 28-60 days after the booster vaccination. The investigators will asess the immunogenicity by seroconversion rate and seropositivity after the booster vaccination, and evaluate the antibody persistence using seropositive rate and GMT in participants before the booster vaccination. Safety will assessed with the occurrence of adverse events reported across the study groups.

Official Title
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Immunogenicity and Safety of the Booster Dose of Polio Vaccine Immunization Using Sabin IPV or bOPV at Children Aged 4 Years With Different Three Sequential Schedules History by Sabin IPV or bOPV in China

Conditions
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Polio, Vaccine Reaction

Intervention / Treatment
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* Biological: vaccinated with Sabin IPV
* Biological: vaccinated with bOPV


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants aged ≥48 months to ≤ 51 months from preliminary study (NCT03147560) with sequential immunization history by Sabin IPV and bOPV. Parent/legal acceptable representative is willing and able to understand the protocol requirements and provide informed consent. ≥ 14 days interval between the last vaccination. Body temperature ≤ 37.2℃. Exclusion Criteria: Known acute illness, severe chronic disease, acute exacerbation of chronic disease and fever. Known allergy to any constituent of the vaccine. Had 4 doses vaccination record of polio vaccine. Known impairment of immunologic function, or receipt of immunosuppressive therapy or immunoglobulin . Received non-specific immunoglobulin within 1 month. An acute illness with fever (temperature ≥ 37.3℃) or any infectious diseases. Patients with a well-diagnosed history of thrombocytopenia or other coagulation disorders that may cause contraindications for injection. Any condition which, in the opinion of the investigator, would pose a health risk to the subject or interfere with the vaccine.

Ages Eligible for Study
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Minimum Age: 48 Months
Maximum Age: 51 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A(Sabin IPV+ bOPV+ bOPV+Sabin IPV)<br>Give the 4th doses of polio vaccine with Sabin IPV for participants in the Group 1 of preliminary study (NCT03147560). | Biological: vaccinated with Sabin IPV<br>* the 4th dose of polio vaccination<br>|
| Experimental: Group B(Sabin IPV+ Sabin IPV+ bOPV+bOPV)<br>Give the 4th doses of polio vaccine with bOPV for participants in the Group 2 of preliminary study (NCT03147560) after randomization. | Biological: vaccinated with bOPV<br>* the 4th dose of polio vaccination<br>|
| Experimental: Group C(Sabin IPV+ Sabin IPV+ bOPV+Sabin IPV)<br>Give the 4th doses of polio vaccine with Sabin IPV for participants in the Group 2 of preliminary study (NCT03147560) after randomization. | Biological: vaccinated with Sabin IPV<br>* the 4th dose of polio vaccination<br>|
| Experimental: Group D(Sabin IPV+ Sabin IPV+ Sabin IPV+bOPV)<br>Give the 4th doses of polio vaccine with bOPV for participants in the Group 3 of preliminary study (NCT03147560) after randomization. | Biological: vaccinated with bOPV<br>* the 4th dose of polio vaccination<br>|
| Experimental: Group E(Sabin IPV+ Sabin IPV+ Sabin IPV+Sabin IPV)<br>Give the 4th doses of polio vaccine with Sabin IPV for participants in the Group 3 of preliminary study (NCT03147560) after randomization. | Biological: vaccinated with Sabin IPV<br>* the 4th dose of polio vaccination<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Seroconversion rates of the booster vaccination | Defined as any positive antibody (titre ≥ 8) response in children who were seronegative prior to the vaccination, or at least a fourfold increase in type-specific antibody levels for children who had pre-existing positive antibodies | before and 28-60 days after the booster dose (4 years old) of polio vaccine | 
| Persistence (tite rates) of antibodies against poliovirus 3 years after the primary 3 dose polio vaccine immunization | The percentage of participants with positive antibody(titre ≥ 8) against all three serotypes of poliovirus 3 years after the primary immunization with different sequential immunization schedules using sIPV or bOPV | 3 years after the primary three doses of polio immunization(before the booster vaccination ) | 
| Seroprotection rates after the booster vaccination | The percentage of participants with positive antibody(titre ≥ 8) against all three serotypes of poliovirus | 28-60 days after the booster dose (4 years old) of polio vaccine | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of the booster dose of polio vaccine immunization | the occurrence of adverse events for the booster dose of Polio vaccine administered at age 4 using Sabin IPV or bOPV | 30 days after the booster vaccination | 
| Antibody titers pesistence against poliovirus | Geometric Mean Titres (GMTs) or Median antibody titers for three poliovirus types | 3 years after the primary three doses of polio immunization(before the booster vaccination ) | 
| Antibody titers against poliovirus after the booster immunization | Geometric Mean Titres (GMTs) or Median antibody titers for three poliovirus types after the booster dose of Polio vaccine administered at age 4 using Sabin IPV or bOPV | 28-60 days after the booster dose of polio vaccine given | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Immunogenicity, Antibody persistence, Safety, Sabin IPV, bOPV