<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03821441</url>
  </required_header>
  <id_info>
    <org_study_id>201518502-C（bOPV-PRO-C）</org_study_id>
    <nct_id>NCT03821441</nct_id>
  </id_info>
  <brief_title>Trail To Evaluate the Immune Effects of Primary and Booster Immunizations With Poliovirus Vaccine</brief_title>
  <official_title>Trail To Evaluate the Immunity Duration of Different Sequential Immunization Schedules and Effectiveness for Bivalent Oral Poliomyelitis Vaccine Co-administered With IPV Booster Immunization for Poliovirus Vaccine</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Cancer Institute and Hospital, Chinese Academy of Medical Sciences</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Guangxi Center for Disease Control and Prevention</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Cancer Institute and Hospital, Chinese Academy of Medical Sciences</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Trail To Evaluate the Immunity Duration of healthy children who already took part in &quot; The&#xD;
      safety and immunogenicity by different sequential schedules of bOPV and bOPV in dragee candy&#xD;
      with sIPV, a randomized, double blind, single center and parallel phase Ⅲ clinic trial was&#xD;
      performed in Infants of two-month old in Guangxi Province, China&quot; and continue to search for&#xD;
      the effects of booster immunization.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      According to the requirement of the Strategy of Polio Eradication &amp; Endgame Strategic Plan&#xD;
      2013-2018, bivalent oral attenuated live poliomyelitis vaccine against type 1 and 3 (bOPV)&#xD;
      and inactivated poliomyelitis vaccine made by Sabin strain (sIPV) need to be used to&#xD;
      eradiation both the wild poliovirus and vaccine-derived poliovirus. To evaluate the safety&#xD;
      and immunogenicity by different sequential immunization schedules of bOPV and bOPV in dragee&#xD;
      candy with sIPV,a randomized, double blind, single center and parallel phase Ⅲ clinic trial&#xD;
      was performed in Guangxi Province in China. A total of 1200 infants at 2 months old were&#xD;
      selected, and randomlydivided into 12 different groups (100 individuals were included in each&#xD;
      group) administrated the vaccines at 0, 28, 56 days schedule.The detail of each group as&#xD;
      following:1)1-dose cIPV + 2-dose bOPV (Candy); 2)1-dose sIPV + 2-dose bOPV (Candy); 3)2-dose&#xD;
      cIPV + 1-dose bOPV (Candy); 4)2-dose sIPV + 1-dose bOPV (Candy); 5)2-dose cIPV + 1-dose tOPV&#xD;
      (Candy); 6)2-dose sIPV + 1-dose tOPV (Candy); 7)1-dose cIPV + 2-dose bOPV (Liquid); 8)1-dose&#xD;
      sIPV + 2-dose bOPV (Liquid); 9)2-dose cIPV + 1-dose bOPV (Liquid); 10)2-dose sIPV + 1-dose&#xD;
      bOPV (Liquid); 11)2-dose cIPV + 1-dose tOPV (Liquid); 12)2-dose sIPV + 1-dose tOPV&#xD;
      (Liquid).Blood Sample was collected before vaccination and one month after the third dose of&#xD;
      vaccination. Neutralization antibody against type I, Type I and Type III poliomyelitis virus&#xD;
      were detected to evaluate the seroprotection rates and antibody geometric mean&#xD;
      concentrations. The fecal samples were collected to test viral shedding.The safety by&#xD;
      different sequential schedule of the vaccines was also evaluated.This part of study have&#xD;
      already been done in 2016.&#xD;
&#xD;
      To further evaluate the immunity duration of different sequential immunization schedules for&#xD;
      bOPV and IPV ,more importantly,trying to research the effectiveness of bOPV booster&#xD;
      immunization,the previous study will continue.&#xD;
&#xD;
      The detail of the research as following:&#xD;
&#xD;
      The subject, who have already receipted 3-dose polio vaccine for primary immunization in&#xD;
      phase III clinical trail in Guangxi and with the result of the paired-serum, are recruited&#xD;
      again.In order to research the immunity durability of primary immunizations of primary&#xD;
      immunization(3 doses of immunization),blood samples are collected from the subject aged 24&#xD;
      months,36 months and 48 months separately.Neutralization antibody titers for against type I,&#xD;
      Type I and Type III poliomyelitis virus are detected,moreover,the positive rate and antibody&#xD;
      geometric mean titers are analyzed.&#xD;
&#xD;
      A single dose of bOPV（liquid/candy) will be given orally to subjects at the age of 48 months&#xD;
      which can in support of the effectiveness research of booster immunization with bOPV. To&#xD;
      protect the rights and interests of subjects,the investigator can use other poliovirus&#xD;
      vaccine such as IPV instead when bOPV（liquid/candy）is not available.&#xD;
&#xD;
      The anticoagulant blood will be collected separatly at 48 months and the 28 days after&#xD;
      booster immunization from subjects,which will be used to detect cellular immune response.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">January 4, 2018</start_date>
  <completion_date type="Anticipated">August 2020</completion_date>
  <primary_completion_date type="Anticipated">May 2020</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Positive rate of anti-poliovirus antibodies.</measure>
    <time_frame>at aged 24 months</time_frame>
    <description>To evaluate the effectiveness of bivalent oral attenuated live poliomyelitis vaccine against type 1 and type 3 (Human Diploid Cell) (candy/liquid) co-administered with co-administered IPV by neutralization assay. Defined ≥ 8 (1/dil) for anti-poliovirus as positive.These data is used to calculate positive rate of anti-poliovirus antibodies.When anti-poliovirus antibodies level ≥ 8 (1/dil),there is protective effect on subjects.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Positive rate of anti-poliovirus antibodies.</measure>
    <time_frame>at aged 36 months</time_frame>
    <description>To evaluate the effectiveness of bivalent oral attenuated live poliomyelitis vaccine against type 1 and type 3 (Human Diploid Cell) (candy/liquid) co-administered with co-administered IPV by neutralization assay. Defined ≥ 8 (1/dil) for anti-poliovirus as positive.These data is used to calculate positive rate of anti-poliovirus antibodies.When anti-poliovirus antibodies level ≥ 8 (1/dil),there is protective effect on subjects.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Positive rate of anti-poliovirus antibodies.</measure>
    <time_frame>at aged 48 months</time_frame>
    <description>To evaluate the effectiveness of bivalent oral attenuated live poliomyelitis vaccine against type 1 and type 3 (Human Diploid Cell) (candy/liquid) co-administered with co-administered IPV by neutralization assay. Defined ≥ 8 (1/dil) for anti-poliovirus as positive.These data is used to calculate positive rate of anti-poliovirus antibodies.When anti-poliovirus antibodies level ≥ 8 (1/dil),there is protective effect on subjects.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The GMT and of positive rate anti-poliovirus antibodies in different age.</measure>
    <time_frame>at aged 24、36、48 months</time_frame>
    <description>In order to know the duration of anti-poliovirus antibodies level.We will use the neutralization assay to research the duration of anti-poliovirus antibodies types1, 2, and 3 induced by bivalent oral attenuated live poliomyelitis vaccine against type 1 and type 3 (Human Diploid Cell) (candy/liquid) co-administered with IPV.Using the method of neutralization assay. Defined ≥ 8 (1/dil) for anti-Poliovirus as positive.The data are used to analysis the GMT 、 positive rate of poliovirus antibodies.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The adverse reaction and event of polio vaccine occur in subjects</measure>
    <time_frame>following 28 days after the boosting dose of bOPV</time_frame>
    <description>Local and systemic adverse events were active collected in subjects after boosting dose of bOPV.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The GMT 、seroconversion rate of poliovirus antibodies after booster immunization.</measure>
    <time_frame>at aged 48 months and 28 days after the boosting dose of bOPV</time_frame>
    <description>In order to know the rationality of booster immunization and make sure dose the subject need a booster immunization and when is the best time.The investigator will give one dose boosting vaccine（bOPV）when the subject aged 48 months.The type of bOPV (liquid/candy) depends on what kind of vaccine the child had eaten in&quot; Randomized, Double Blind, Single Center, Parallel Trial to Evaluate the Safety and Immunogenicity by Different Sequential Immunization Schedules of Bivalent Oral Poliomyelitis Vaccine Co-administered With IPV in Infants Aged 2 Months.&quot; Using the method of neutralization assay to detect the poliovirus antibodies，defined ≥ 8 (1/dil) for anti-Poliovirus as positive.The data are used to analysis the GMT 、seroconversion rate of poliovirus antibodies.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cellular immunity situation in booster immunization</measure>
    <time_frame>at aged 48 months and 28 days after the boosting dose of bOPV</time_frame>
    <description>The anticoagulant blood will be collected separatly at 48 months and the 28 days after booster immunization from subjects,which will be used to detect cellular immune response. The blood were measured by flow cytometry,luminex or microarray,etc.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">1165</enrollment>
  <condition>Poliomyelitis</condition>
  <arm_group>
    <arm_group_label>bOPV(Candy)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>bOPV (Candy): bivalent oral attenuated live poliomyelitis vaccine against type 1 and type 3 in Dragee Candy (Human Diploid Cell) Produced by Institute of Medical Biology, Chinese Academy of Medical Sciences.&#xD;
1g/pill,10 pills/pach,one pill each time; each pill containing polio virus≥5.92 lgCCID50 including type1 polio virus≥5.8 lgCCID50，type 3 polio virus ≥5.3lgCCID50.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>bOPV(Liquid)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>bOPV (Liquid): bivalent oral attenuated live poliomyelitis vaccine against type 1 and type 3 (Human Diploid Cell) Produced by Institute of Medical Biology, Chinese Academy of Medical Sciences.&#xD;
0.5ml or 1.0ml each bottle;total content of polio virus≥7.12lgCCID50/ml，type1 polio virus≥7.0 lgCCID50/ml，type 3 polio virus ≥6.5lgCCID50/ml.(2 drops each person;be be equivalent to 0.1ml each person )</description>
  </arm_group>
  <arm_group>
    <arm_group_label>bOPV（liquid）</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>bOPV(Liquid):Poliomyelitis (Live) Vaccine Type I Type III (Human Diploid Cell), Oral Produced by Beijing Tiantan Biological Products Co., Ltd. 1.0ml each bottle,2 drops each person(be be equivalent to 0.1ml each person).(total content of polio virus≥6.12lgCCID50，type1 polio virus≥6.0 lgCCID50，type 3 polio virus ≥5.5lgCCID50 in each 0.1 ml)</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>bOPV(Candy)</intervention_name>
    <description>A single dose of 1 pill orally of bOPV to subjects aged 48 months who recieved bOPV (candy) produced by institute of Medical Biology, Chinese Academy of Medical Sciences in primary immunization.&#xD;
If bOPV(candy/liquid) is not available ,in order to protect the rights and interests of subjects ,the investigator can adjust other poliovirus vaccine such as IPV replace bOPV.</description>
    <arm_group_label>bOPV(Candy)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>bOPV(Liquid)</intervention_name>
    <description>A single dose of 2 drops (0.1 ml) orally of bOPV to subjects aged 48 months who recieved bOPV (liquid) produced by institute of Medical Biology, Chinese Academy of Medical Sciences in primary immunization.&#xD;
If bOPV(candy/liquid) is not available,in order to protect the rights and interests of subjects ,the investigator can adjust other poliovirus vaccine such as IPV replace bOPV.</description>
    <arm_group_label>bOPV(Liquid)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>bOPV(Liquid)</intervention_name>
    <description>A single dose of 2 drops (0.1 ml) orally of bOPV to subjects aged 48 months who received tOPV (liquid) produced by Beijing Tiantan Biological Products Co., Ltd. in primary immunization.&#xD;
If bOPV(candy/liquid) is not available,in order to protect the rights and interests of subjects ,the investigator can adjust other poliovirus vaccine such as IPV replace bOPV.</description>
    <arm_group_label>bOPV（liquid）</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subjects who have already taken part in phase 3 clinical trail in Guangxi and were&#xD;
             vaccinated 3-dose primary immunization with polio vaccines .Moreover，the results of&#xD;
             the selected paired serum are required.&#xD;
&#xD;
          -  24 months old(calendar month).&#xD;
&#xD;
          -  Guardians understand the contents and requirements of this trail , meanwhile,&#xD;
             voluntarily joined this study with informed consents.&#xD;
&#xD;
          -  Able to attend all scheduled visits and to comply with all trial procedures(including&#xD;
             vaccinate and blood collection)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any booster immunization with polio vaccine after finishing 3-dose primary&#xD;
             immunizations research.&#xD;
&#xD;
          -  Polio virus infection was demonstrated in laboratory experiment.&#xD;
&#xD;
          -  Participation in another clinical trial at the same times.&#xD;
&#xD;
          -  Any condition that in the opinion of the investigator, may interfere with the&#xD;
             evaluation of study objectives or increase the risk of subjects,such as acute or&#xD;
             chronic diseases 、some abnormal detected by lab,and so on.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>24 Months</minimum_age>
    <maximum_age>48 Months</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Zhaojun Mo, Master</last_name>
    <role>Principal Investigator</role>
    <affiliation>Guangxi Province Center for Diseases Control and Prevention</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Jingsi Yang, Master</last_name>
    <phone>+8687168334986</phone>
    <email>yjs@imbcams.com.cn</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Jing Li, Master</last_name>
    <phone>13888865251</phone>
    <email>sola@imbcams.com.cn</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Guangxi Provincial Center for Diseases Control and Prevention</name>
      <address>
        <city>Nanning</city>
        <state>Guangxi</state>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Zhaojun Mo, Master</last_name>
    </contact>
    <investigator>
      <last_name>Zhaojun Mo, Master</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>May 2018</verification_date>
  <study_first_submitted>January 3, 2019</study_first_submitted>
  <study_first_submitted_qc>January 28, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 29, 2019</study_first_posted>
  <last_update_submitted>January 28, 2019</last_update_submitted>
  <last_update_submitted_qc>January 28, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 29, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Cancer Institute and Hospital, Chinese Academy of Medical Sciences</investigator_affiliation>
    <investigator_full_name>Jingsi Yang</investigator_full_name>
    <investigator_title>Director</investigator_title>
  </responsible_party>
  <keyword>bOPV</keyword>
  <keyword>IPV</keyword>
  <keyword>Sequential immunization</keyword>
  <keyword>Immunity Duration</keyword>
  <keyword>Booster Immunization</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Poliomyelitis</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03821441
org study id: 201518502-C（bOPV-PRO-C）
nct id: NCT03821441
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Trail To Evaluate the Immunity Duration of healthy children who already took part in " The
      safety and immunogenicity by different sequential schedules of bOPV and bOPV in dragee candy
      with sIPV, a randomized, double blind, single center and parallel phase Ⅲ clinic trial was
      performed in Infants of two-month old in Guangxi Province, China" and continue to search for
      the effects of booster immunization.
According to the requirement of the Strategy of Polio Eradication & Endgame Strategic Plan
      2013-2018, bivalent oral attenuated live poliomyelitis vaccine against type 1 and 3 (bOPV)
      and inactivated poliomyelitis vaccine made by Sabin strain (sIPV) need to be used to
      eradiation both the wild poliovirus and vaccine-derived poliovirus. To evaluate the safety
      and immunogenicity by different sequential immunization schedules of bOPV and bOPV in dragee
      candy with sIPV,a randomized, double blind, single center and parallel phase Ⅲ clinic trial
      was performed in Guangxi Province in China. A total of 1200 infants at 2 months old were
      selected, and randomlydivided into 12 different groups (100 individuals were included in each
      group) administrated the vaccines at 0, 28, 56 days schedule.The detail of each group as
      following:1)1-dose cIPV + 2-dose bOPV (Candy); 2)1-dose sIPV + 2-dose bOPV (Candy); 3)2-dose
      cIPV + 1-dose bOPV (Candy); 4)2-dose sIPV + 1-dose bOPV (Candy); 5)2-dose cIPV + 1-dose tOPV
      (Candy); 6)2-dose sIPV + 1-dose tOPV (Candy); 7)1-dose cIPV + 2-dose bOPV (Liquid); 8)1-dose
      sIPV + 2-dose bOPV (Liquid); 9)2-dose cIPV + 1-dose bOPV (Liquid); 10)2-dose sIPV + 1-dose
      bOPV (Liquid); 11)2-dose cIPV + 1-dose tOPV (Liquid); 12)2-dose sIPV + 1-dose tOPV
      (Liquid).Blood Sample was collected before vaccination and one month after the third dose of
      vaccination. Neutralization antibody against type I, Type I and Type III poliomyelitis virus
      were detected to evaluate the seroprotection rates and antibody geometric mean
      concentrations. The fecal samples were collected to test viral shedding.The safety by
      different sequential schedule of the vaccines was also evaluated.This part of study have
      already been done in 2016.

      To further evaluate the immunity duration of different sequential immunization schedules for
      bOPV and IPV ,more importantly,trying to research the effectiveness of bOPV booster
      immunization,the previous study will continue.

      The detail of the research as following:

      The subject, who have already receipted 3-dose polio vaccine for primary immunization in
      phase III clinical trail in Guangxi and with the result of the paired-serum, are recruited
      again.In order to research the immunity durability of primary immunizations of primary
      immunization(3 doses of immunization),blood samples are collected from the subject aged 24
      months,36 months and 48 months separately.Neutralization antibody titers for against type I,
      Type I and Type III poliomyelitis virus are detected,moreover,the positive rate and antibody
      geometric mean titers are analyzed.

      A single dose of bOPV（liquid/candy) will be given orally to subjects at the age of 48 months
      which can in support of the effectiveness research of booster immunization with bOPV. To
      protect the rights and interests of subjects,the investigator can use other poliovirus
      vaccine such as IPV instead when bOPV（liquid/candy）is not available.

      The anticoagulant blood will be collected separatly at 48 months and the 28 days after
      booster immunization from subjects,which will be used to detect cellular immune response.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Positive rate of anti-poliovirus antibodies.
time frame: at aged 24 months
description: To evaluate the effectiveness of bivalent oral attenuated live poliomyelitis vaccine against type 1 and type 3 (Human Diploid Cell) (candy/liquid) co-administered with co-administered IPV by neutralization assay. Defined ≥ 8 (1/dil) for anti-poliovirus as positive.These data is used to calculate positive rate of anti-poliovirus antibodies.When anti-poliovirus antibodies level ≥ 8 (1/dil),there is protective effect on subjects.
measure: Positive rate of anti-poliovirus antibodies.
time frame: at aged 36 months
description: To evaluate the effectiveness of bivalent oral attenuated live poliomyelitis vaccine against type 1 and type 3 (Human Diploid Cell) (candy/liquid) co-administered with co-administered IPV by neutralization assay. Defined ≥ 8 (1/dil) for anti-poliovirus as positive.These data is used to calculate positive rate of anti-poliovirus antibodies.When anti-poliovirus antibodies level ≥ 8 (1/dil),there is protective effect on subjects.
measure: Positive rate of anti-poliovirus antibodies.
time frame: at aged 48 months
description: To evaluate the effectiveness of bivalent oral attenuated live poliomyelitis vaccine against type 1 and type 3 (Human Diploid Cell) (candy/liquid) co-administered with co-administered IPV by neutralization assay. Defined ≥ 8 (1/dil) for anti-poliovirus as positive.These data is used to calculate positive rate of anti-poliovirus antibodies.When anti-poliovirus antibodies level ≥ 8 (1/dil),there is protective effect on subjects.
measure: The GMT and of positive rate anti-poliovirus antibodies in different age.
time frame: at aged 24、36、48 months
description: In order to know the duration of anti-poliovirus antibodies level.We will use the neutralization assay to research the duration of anti-poliovirus antibodies types1, 2, and 3 induced by bivalent oral attenuated live poliomyelitis vaccine against type 1 and type 3 (Human Diploid Cell) (candy/liquid) co-administered with IPV.Using the method of neutralization assay. Defined ≥ 8 (1/dil) for anti-Poliovirus as positive.The data are used to analysis the GMT 、 positive rate of poliovirus antibodies.
measure: The adverse reaction and event of polio vaccine occur in subjects
time frame: following 28 days after the boosting dose of bOPV
description: Local and systemic adverse events were active collected in subjects after boosting dose of bOPV.
measure: The GMT 、seroconversion rate of poliovirus antibodies after booster immunization.
time frame: at aged 48 months and 28 days after the boosting dose of bOPV
description: In order to know the rationality of booster immunization and make sure dose the subject need a booster immunization and when is the best time.The investigator will give one dose boosting vaccine（bOPV）when the subject aged 48 months.The type of bOPV (liquid/candy) depends on what kind of vaccine the child had eaten in" Randomized, Double Blind, Single Center, Parallel Trial to Evaluate the Safety and Immunogenicity by Different Sequential Immunization Schedules of Bivalent Oral Poliomyelitis Vaccine Co-administered With IPV in Infants Aged 2 Months." Using the method of neutralization assay to detect the poliovirus antibodies，defined ≥ 8 (1/dil) for anti-Poliovirus as positive.The data are used to analysis the GMT 、seroconversion rate of poliovirus antibodies.
measure: Cellular immunity situation in booster immunization
time frame: at aged 48 months and 28 days after the boosting dose of bOPV
description: The anticoagulant blood will be collected separatly at 48 months and the 28 days after booster immunization from subjects,which will be used to detect cellular immune response. The blood were measured by flow cytometry,luminex or microarray,etc.
arm group label: bOPV(Candy)
arm group type: Experimental
description: bOPV (Candy): bivalent oral attenuated live poliomyelitis vaccine against type 1 and type 3 in Dragee Candy (Human Diploid Cell) Produced by Institute of Medical Biology, Chinese Academy of Medical Sciences.
1g/pill,10 pills/pach,one pill each time; each pill containing polio virus≥5.92 lgCCID50 including type1 polio virus≥5.8 lgCCID50，type 3 polio virus ≥5.3lgCCID50.
arm group label: bOPV(Liquid)
arm group type: Experimental
description: bOPV (Liquid): bivalent oral attenuated live poliomyelitis vaccine against type 1 and type 3 (Human Diploid Cell) Produced by Institute of Medical Biology, Chinese Academy of Medical Sciences.
0.5ml or 1.0ml each bottle;total content of polio virus≥7.12lgCCID50/ml，type1 polio virus≥7.0 lgCCID50/ml，type 3 polio virus ≥6.5lgCCID50/ml.(2 drops each person;be be equivalent to 0.1ml each person )
arm group label: bOPV（liquid）
arm group type: Experimental
description: bOPV(Liquid):Poliomyelitis (Live) Vaccine Type I Type III (Human Diploid Cell), Oral Produced by Beijing Tiantan Biological Products Co., Ltd. 1.0ml each bottle,2 drops each person(be be equivalent to 0.1ml each person).(total content of polio virus≥6.12lgCCID50，type1 polio virus≥6.0 lgCCID50，type 3 polio virus ≥5.5lgCCID50 in each 0.1 ml)
intervention type: Biological
intervention name: bOPV(Candy)
description: A single dose of 1 pill orally of bOPV to subjects aged 48 months who recieved bOPV (candy) produced by institute of Medical Biology, Chinese Academy of Medical Sciences in primary immunization.
If bOPV(candy/liquid) is not available ,in order to protect the rights and interests of subjects ,the investigator can adjust other poliovirus vaccine such as IPV replace bOPV.
arm group label: bOPV(Candy)
intervention type: Biological
intervention name: bOPV(Liquid)
description: A single dose of 2 drops (0.1 ml) orally of bOPV to subjects aged 48 months who recieved bOPV (liquid) produced by institute of Medical Biology, Chinese Academy of Medical Sciences in primary immunization.
If bOPV(candy/liquid) is not available,in order to protect the rights and interests of subjects ,the investigator can adjust other poliovirus vaccine such as IPV replace bOPV.
arm group label: bOPV(Liquid)
intervention type: Biological
intervention name: bOPV(Liquid)
description: A single dose of 2 drops (0.1 ml) orally of bOPV to subjects aged 48 months who received tOPV (liquid) produced by Beijing Tiantan Biological Products Co., Ltd. in primary immunization.
If bOPV(candy/liquid) is not available,in order to protect the rights and interests of subjects ,the investigator can adjust other poliovirus vaccine such as IPV replace bOPV.
arm group label: bOPV（liquid）
criteria: 
gender: All
minimum age: 24 Months
maximum age: 48 Months
healthy volunteers: Accepts Healthy Volunteers
last name: Zhaojun Mo, Master
role: Principal Investigator
affiliation: Guangxi Province Center for Diseases Control and Prevention
last name: Jingsi Yang, Master
phone: +8687168334986
email: yjs@imbcams.com.cn
last name: Jing Li, Master
phone: 13888865251
email: sola@imbcams.com.cn
facility: 
status: Recruiting
contact: 
investigator: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
investigator full name: Jingsi Yang
investigator title: Director
mesh term: Poliomyelitis