<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/NCT02990182</url>
  </required_header>
  <id_info>
    <org_study_id>CPqRR - M 02</org_study_id>
    <nct_id>NCT02990182</nct_id>
  </id_info>
  <brief_title>Complementary Study of the Duration of Post-vaccination Against Yellow Fever Immunity in Children</brief_title>
  <official_title>Complementary Study of the Duration of Post-vaccination Against Yellow Fever Immunity in Children</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Oswaldo Cruz Foundation</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Oswaldo Cruz Foundation</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      In a previous study by the researchers' group, the researchers' investigate the duration of&#xD;
      yellow fever post-vaccination immunity in vaccinated children between 9 and 23 months of age.&#xD;
      However, in this study, samples of children in the pre-vaccine period, also known as&#xD;
      unvaccinated children samples (NV) have not been investigated. It is believed that to seek&#xD;
      evidence about the immune status in the medium and long term after vaccination against yellow&#xD;
      fever is necessary to investigate paired samples of children not vaccinated (NV), with&#xD;
      re-evaluation 30-45 days after primary vaccination. The proposed study is to consolidate&#xD;
      aspects of humoral (neutralizing antibodies) and cellular (phenotypic and functional&#xD;
      parameters of T cells and memory B) by means of complementary longitudinal investigation&#xD;
      children, 9-23 months old, unvaccinated (NV) and 30-45 days after primary vaccination.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A sample of 60 children aged 9 to 23 months paired in the pre-vaccine period (NV) and 30-45&#xD;
      post-primary vaccination days will be selected at health facilities in the metropolitan&#xD;
      region of Belo Horizonte.&#xD;
&#xD;
      Children whose mothers consent to participate in research, have collected blood and elements&#xD;
      of past medical history recorded. Analyses of humoral and cellular biomarkers will be used in&#xD;
      a comparative study with other post-vaccination periods previously analyzed in children&#xD;
      during the first phase in study funded by the Ministry of Health.&#xD;
&#xD;
      specific objectives:&#xD;
&#xD;
        1. Estimate and compare the proportion of positivity and the geometric mean plasma titers&#xD;
           of neutralizing antibodies against yellow fever;&#xD;
&#xD;
        2. Assess lymphocyte frequency T and B memory induced in vitro by the vaccine antigen 17DD&#xD;
           substrains, and...&#xD;
&#xD;
        3. Quantify the lymphocytes T CD8 + producers of intracytoplasmic cytokines induced in&#xD;
           vitro by the vaccine antigen 17DD substrains in unvaccinated children and primed aged&#xD;
           between 9 and 23 months, categorized according to the vaccination time 30-45 days.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date>April 2015</start_date>
  <completion_date type="Anticipated">December 2017</completion_date>
  <primary_completion_date type="Actual">April 2017</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Quantification of Humoral and cellular immunity after first yellow fever vaccination</measure>
    <time_frame>Time 0 (immediately before) and Time 1 (30-45 days after) primary vaccination against yellow fever</time_frame>
    <description>Consolidating aspects of humoral (quantification of neutralizing antibodies - &gt;2.log10IU/mL) and cellular (Percentege of phenotypic and functional parameters of T cells and B memory) through a complementary longitudinal investigation in children aged 9 to 23 month old unvaccinated and 30-45 days after first vaccination .</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Quantification of titers of neutralizing antibodies in plasma samples</measure>
    <time_frame>Time 0 (immediately before) and Time 1 (30-45 days after) primary vaccination against yellow fever</time_frame>
    <description>Quantify the titers of neutralizing antibodies against yellow fever immediately before and 30-45 days after primary vaccination against yellow fever in children 9-23 months of age without yellow fever vaccination history.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluate the frequency (percentage) of T cells and B memory induced in vitro by the vaccine antigen 17DD</measure>
    <time_frame>Time 0 (immediately before) and Time 1 (30-45 days after) primary vaccination against yellow fever</time_frame>
    <description>Evaluate the frequency (percentage) of T cells and B memory induced in vitro by the vaccine antigen 17DD immediately before and 30-45 days after primary vaccination against yellow fever in children 9-23 months old with no vaccination history against yellow fever.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluate the frequency (percentage) of T and B cells expressing intracytoplasmic cytokines in vitro induced by the vaccine antigen 17DD</measure>
    <time_frame>Time 0 (immediately before) and Time 1 (30-45 days after) primary vaccination against yellow fever</time_frame>
    <description>Evaluate the frequency (percentage) of T and B cells expressing intracytoplasmic cytokines (gama interferon; IL-5, alfa-TNF) CD8 + T lymphocytes, in vitro induced by the vaccine antigen 17DD immediately before and 30-45 days after primary vaccination against yellow fever, in children 9-23 months of age without yellow fever vaccination history.</description>
  </secondary_outcome>
  <enrollment type="Actual">60</enrollment>
  <condition>Yellow Fever</condition>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      whole blood and plasma&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        The study provides immunoassays paired before and after anti-yellow fever vaccination in&#xD;
        children of both sexes, of any color, class or social group. This will be necessary 60&#xD;
        paired samples (pre-vaccine period and 30-45 days after primary vaccination) of children&#xD;
        aged 9 to 23 months, living in areas where YF vaccine makes up the basic immunization&#xD;
        calendar and will receive the vaccine in the routine of UBRs in the first two years of&#xD;
        life. This study will be conducted with samples collected from children living in Ribeirão&#xD;
        das Neves - Minas Gerais. It will be collected 7 mL of whole blood collected in Heparin&#xD;
        Sodium. It will be allowed to make two attempts to collect only. These samples will be used&#xD;
        for the realization of the humoral and cellular immunity study.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Will be eligible for the study:&#xD;
&#xD;
          -  children 9-23 months of age;&#xD;
&#xD;
          -  both sexes;&#xD;
&#xD;
          -  children who will be vaccinated against yellow fever, whose parents or guardians sign&#xD;
             the consent form.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  children who received another vaccine within 30 days before or after the yellow fever&#xD;
             vaccine;&#xD;
&#xD;
          -  children which have permanent or temporary immunosuppression, including those treated&#xD;
             with corticosteroids at doses higher than 2 mg / kg, and those with disease autoimmune&#xD;
             diseases, transient or permanent immunosuppression induced diseases (cancer, AIDS,&#xD;
             etc.) or treatment (immunosuppressive drugs, radiotherapy, etc.). Corticosteroids&#xD;
             (such as prednisone, dexamethasone) for less than two weeks, or by inhalation or&#xD;
             topical use, do not indicate exclusion from the study, but must be registered in the&#xD;
             questionnaire (Annex II);&#xD;
&#xD;
          -  children with hemoglobinopathies;&#xD;
&#xD;
          -  children with a history of blood transfusion or treatment with hyperimmune serum up to&#xD;
             90 days prior to blood collection.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>9 Months</minimum_age>
    <maximum_age>23 Months</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Olindo A Martins-Filho, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Centro de Pesquisas René Rachou</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Centro de Pesquisas René Rachou</name>
      <address>
        <city>Belo Horizonte</city>
        <state>Minas Gerais</state>
        <zip>30190002</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <link>
    <url>http://www.who.int/</url>
    <description>World Health Organization.International health regulations (2005)</description>
  </link>
  <link>
    <url>http://portalsaude.saude.gov.br/</url>
    <description>Ministério da Saúde. Secretaria de Vigilância em Saúde. Departamento de Vigilância Epidemiológica. Guia de Vigilância Epidemiológica. 6ª edição. Série A. Normas e Manuais Técnicos. Brasília - DF, 2005.</description>
  </link>
  <reference>
    <citation>Vasconcelos PF. [Yellow Fever]. Rev Soc Bras Med Trop. 2003 Mar-Apr;36(2):275-93. doi: 10.1590/s0037-86822003000200012. Epub 2003 Jun 10. Portuguese.</citation>
    <PMID>12806465</PMID>
  </reference>
  <results_reference>
    <citation>ANDERSON CR, GAST-GALVIS A. Immunity to yellow fever five years after vaccination. Am J Hyg. 1947 May;45(3):302-4. doi: 10.1093/oxfordjournals.aje.a119138. No abstract available.</citation>
    <PMID>20240017</PMID>
  </results_reference>
  <results_reference>
    <citation>Belmusto-Worn VE, Sanchez JL, McCarthy K, Nichols R, Bautista CT, Magill AJ, Pastor-Cauna G, Echevarria C, Laguna-Torres VA, Samame BK, Baldeon ME, Burans JP, Olson JG, Bedford P, Kitchener S, Monath TP. Randomized, double-blind, phase III, pivotal field trial of the comparative immunogenicity, safety, and tolerability of two yellow fever 17D vaccines (Arilvax and YF-VAX) in healthy infants and children in Peru. Am J Trop Med Hyg. 2005 Feb;72(2):189-97.</citation>
    <PMID>15741556</PMID>
  </results_reference>
  <results_reference>
    <citation>Camacho LA, Freire Mda S, Leal Mda L, Aguiar SG, Nascimento JP, Iguchi T, Lozana Jde A, Farias RH; Collaborative Group for the Study of Yellow Fever Vaccines. Immunogenicity of WHO-17D and Brazilian 17DD yellow fever vaccines: a randomized trial. Rev Saude Publica. 2004 Oct;38(5):671-8. doi: 10.1590/s0034-89102004000500009. Epub 2004 Oct 18.</citation>
    <PMID>15499438</PMID>
  </results_reference>
  <results_reference>
    <citation>Collaborative Group for Studies with Yellow Fever; Camacho LAB. Immunogenicity of 17DD and WHO 17D -213/77 Yellow Fever Vaccines in Children less than 2 years old: a randomized, double-blind study. In: 5th World Congress of the World Society fo Pediatric Infectious Diseases, 2007, Bangkok, Tailandia. Book of Abstracts, 2007.</citation>
  </results_reference>
  <results_reference>
    <citation>Collaborative Group for Studies with Yellow Fever Vaccine. Randomized, double-blind, multicenter study of the immunogenicity and reactogenicity of 17DD and WHO 17D-213/77 yellow fever vaccines in children: implications for the Brazilian National Immunization Program. Vaccine. 2007 Apr 20;25(16):3118-23. doi: 10.1016/j.vaccine.2007.01.053. Epub 2007 Jan 22.</citation>
    <PMID>17316925</PMID>
  </results_reference>
  <results_reference>
    <citation>FOX JP, FONSECA DA CUNHA J, KOSSOBUDZKI SL. Additional observations on the duration of humoral immunity following vaccination with the 17D strain of yellow fever virus. Am J Hyg. 1948 Jan;47(1):64-70. doi: 10.1093/oxfordjournals.aje.a119186. No abstract available.</citation>
    <PMID>18921440</PMID>
  </results_reference>
  <results_reference>
    <citation>Hepburn MJ, Kortepeter MG, Pittman PR, Boudreau EF, Mangiafico JA, Buck PA, Norris SL, Anderson EL. Neutralizing antibody response to booster vaccination with the 17d yellow fever vaccine. Vaccine. 2006 Apr 5;24(15):2843-9. doi: 10.1016/j.vaccine.2005.12.055. Epub 2006 Jan 18.</citation>
    <PMID>16494976</PMID>
  </results_reference>
  <results_reference>
    <citation>Monath TP, Cetron MS &amp; Teuwen DE. Yellow fever vaccine. In Plotkin SA, Orenstein WA &amp; Offit P. Organizadores. Vaccine. Philadelphia. Saunders Elsevier 2008. p. 959-1056.</citation>
  </results_reference>
  <results_reference>
    <citation>Niedrig M, Lademann M, Emmerich P, Lafrenz M. Assessment of IgG antibodies against yellow fever virus after vaccination with 17D by different assays: neutralization test, haemagglutination inhibition test, immunofluorescence assay and ELISA. Trop Med Int Health. 1999 Dec;4(12):867-71. doi: 10.1046/j.1365-3156.1999.00496.x.</citation>
    <PMID>10632996</PMID>
  </results_reference>
  <results_reference>
    <citation>Poland JD, Calisher CH, Monath TP, Downs WG, Murphy K. Persistence of neutralizing antibody 30-35 years after immunization with 17D yellow fever vaccine. Bull World Health Organ. 1981;59(6):895-900.</citation>
    <PMID>6978196</PMID>
  </results_reference>
  <verification_date>July 2017</verification_date>
  <study_first_submitted>September 1, 2015</study_first_submitted>
  <study_first_submitted_qc>December 7, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 13, 2016</study_first_posted>
  <last_update_submitted>July 12, 2017</last_update_submitted>
  <last_update_submitted_qc>July 12, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">July 13, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Oswaldo Cruz Foundation</investigator_affiliation>
    <investigator_full_name>Olindo de Assis Martins Filho</investigator_full_name>
    <investigator_title>PhD</investigator_title>
  </responsible_party>
  <keyword>Yellow Fever Vaccine</keyword>
  <keyword>Immunity, Humoral</keyword>
  <keyword>Immunity, Cellular</keyword>
  <keyword>children</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Yellow Fever</mesh_term>
    <mesh_term>Fever</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/NCT02990182
org study id: CPqRR - M 02
nct id: NCT02990182
lead sponsor: 
has dmc: No
In a previous study by the researchers' group, the researchers' investigate the duration of
      yellow fever post-vaccination immunity in vaccinated children between 9 and 23 months of age.
      However, in this study, samples of children in the pre-vaccine period, also known as
      unvaccinated children samples (NV) have not been investigated. It is believed that to seek
      evidence about the immune status in the medium and long term after vaccination against yellow
      fever is necessary to investigate paired samples of children not vaccinated (NV), with
      re-evaluation 30-45 days after primary vaccination. The proposed study is to consolidate
      aspects of humoral (neutralizing antibodies) and cellular (phenotypic and functional
      parameters of T cells and memory B) by means of complementary longitudinal investigation
      children, 9-23 months old, unvaccinated (NV) and 30-45 days after primary vaccination.
A sample of 60 children aged 9 to 23 months paired in the pre-vaccine period (NV) and 30-45
      post-primary vaccination days will be selected at health facilities in the metropolitan
      region of Belo Horizonte.

      Children whose mothers consent to participate in research, have collected blood and elements
      of past medical history recorded. Analyses of humoral and cellular biomarkers will be used in
      a comparative study with other post-vaccination periods previously analyzed in children
      during the first phase in study funded by the Ministry of Health.

      specific objectives:

        1. Estimate and compare the proportion of positivity and the geometric mean plasma titers
           of neutralizing antibodies against yellow fever;

        2. Assess lymphocyte frequency T and B memory induced in vitro by the vaccine antigen 17DD
           substrains, and...

        3. Quantify the lymphocytes T CD8 + producers of intracytoplasmic cytokines induced in
           vitro by the vaccine antigen 17DD substrains in unvaccinated children and primed aged
           between 9 and 23 months, categorized according to the vaccination time 30-45 days.
observational model: Cohort
time perspective: Prospective
measure: Quantification of Humoral and cellular immunity after first yellow fever vaccination
time frame: Time 0 (immediately before) and Time 1 (30-45 days after) primary vaccination against yellow fever
description: Consolidating aspects of humoral (quantification of neutralizing antibodies - >2.log10IU/mL) and cellular (Percentege of phenotypic and functional parameters of T cells and B memory) through a complementary longitudinal investigation in children aged 9 to 23 month old unvaccinated and 30-45 days after first vaccination .
measure: Quantification of titers of neutralizing antibodies in plasma samples
time frame: Time 0 (immediately before) and Time 1 (30-45 days after) primary vaccination against yellow fever
description: Quantify the titers of neutralizing antibodies against yellow fever immediately before and 30-45 days after primary vaccination against yellow fever in children 9-23 months of age without yellow fever vaccination history.
measure: Evaluate the frequency (percentage) of T cells and B memory induced in vitro by the vaccine antigen 17DD
time frame: Time 0 (immediately before) and Time 1 (30-45 days after) primary vaccination against yellow fever
description: Evaluate the frequency (percentage) of T cells and B memory induced in vitro by the vaccine antigen 17DD immediately before and 30-45 days after primary vaccination against yellow fever in children 9-23 months old with no vaccination history against yellow fever.
measure: Evaluate the frequency (percentage) of T and B cells expressing intracytoplasmic cytokines in vitro induced by the vaccine antigen 17DD
time frame: Time 0 (immediately before) and Time 1 (30-45 days after) primary vaccination against yellow fever
description: Evaluate the frequency (percentage) of T and B cells expressing intracytoplasmic cytokines (gama interferon; IL-5, alfa-TNF) CD8 + T lymphocytes, in vitro induced by the vaccine antigen 17DD immediately before and 30-45 days after primary vaccination against yellow fever, in children 9-23 months of age without yellow fever vaccination history.
whole blood and plasma
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 9 Months
maximum age: 23 Months
healthy volunteers: Accepts Healthy Volunteers
last name: Olindo A Martins-Filho, PhD
role: Principal Investigator
affiliation: Centro de Pesquisas René Rachou
facility: 
country: Brazil
url: http://www.who.int/
description: World Health Organization.International health regulations (2005)
url: http://portalsaude.saude.gov.br/
description: Ministério da Saúde. Secretaria de Vigilância em Saúde. Departamento de Vigilância Epidemiológica. Guia de Vigilância Epidemiológica. 6ª edição. Série A. Normas e Manuais Técnicos. Brasília - DF, 2005.
citation: Vasconcelos PF. [Yellow Fever]. Rev Soc Bras Med Trop. 2003 Mar-Apr;36(2):275-93. doi: 10.1590/s0037-86822003000200012. Epub 2003 Jun 10. Portuguese.
PMID: 12806465
citation: ANDERSON CR, GAST-GALVIS A. Immunity to yellow fever five years after vaccination. Am J Hyg. 1947 May;45(3):302-4. doi: 10.1093/oxfordjournals.aje.a119138. No abstract available.
PMID: 20240017
citation: Belmusto-Worn VE, Sanchez JL, McCarthy K, Nichols R, Bautista CT, Magill AJ, Pastor-Cauna G, Echevarria C, Laguna-Torres VA, Samame BK, Baldeon ME, Burans JP, Olson JG, Bedford P, Kitchener S, Monath TP. Randomized, double-blind, phase III, pivotal field trial of the comparative immunogenicity, safety, and tolerability of two yellow fever 17D vaccines (Arilvax and YF-VAX) in healthy infants and children in Peru. Am J Trop Med Hyg. 2005 Feb;72(2):189-97.
PMID: 15741556
citation: Camacho LA, Freire Mda S, Leal Mda L, Aguiar SG, Nascimento JP, Iguchi T, Lozana Jde A, Farias RH; Collaborative Group for the Study of Yellow Fever Vaccines. Immunogenicity of WHO-17D and Brazilian 17DD yellow fever vaccines: a randomized trial. Rev Saude Publica. 2004 Oct;38(5):671-8. doi: 10.1590/s0034-89102004000500009. Epub 2004 Oct 18.
PMID: 15499438
citation: Collaborative Group for Studies with Yellow Fever; Camacho LAB. Immunogenicity of 17DD and WHO 17D -213/77 Yellow Fever Vaccines in Children less than 2 years old: a randomized, double-blind study. In: 5th World Congress of the World Society fo Pediatric Infectious Diseases, 2007, Bangkok, Tailandia. Book of Abstracts, 2007.
citation: Collaborative Group for Studies with Yellow Fever Vaccine. Randomized, double-blind, multicenter study of the immunogenicity and reactogenicity of 17DD and WHO 17D-213/77 yellow fever vaccines in children: implications for the Brazilian National Immunization Program. Vaccine. 2007 Apr 20;25(16):3118-23. doi: 10.1016/j.vaccine.2007.01.053. Epub 2007 Jan 22.
PMID: 17316925
citation: FOX JP, FONSECA DA CUNHA J, KOSSOBUDZKI SL. Additional observations on the duration of humoral immunity following vaccination with the 17D strain of yellow fever virus. Am J Hyg. 1948 Jan;47(1):64-70. doi: 10.1093/oxfordjournals.aje.a119186. No abstract available.
PMID: 18921440
citation: Hepburn MJ, Kortepeter MG, Pittman PR, Boudreau EF, Mangiafico JA, Buck PA, Norris SL, Anderson EL. Neutralizing antibody response to booster vaccination with the 17d yellow fever vaccine. Vaccine. 2006 Apr 5;24(15):2843-9. doi: 10.1016/j.vaccine.2005.12.055. Epub 2006 Jan 18.
PMID: 16494976
citation: Monath TP, Cetron MS & Teuwen DE. Yellow fever vaccine. In Plotkin SA, Orenstein WA & Offit P. Organizadores. Vaccine. Philadelphia. Saunders Elsevier 2008. p. 959-1056.
citation: Niedrig M, Lademann M, Emmerich P, Lafrenz M. Assessment of IgG antibodies against yellow fever virus after vaccination with 17D by different assays: neutralization test, haemagglutination inhibition test, immunofluorescence assay and ELISA. Trop Med Int Health. 1999 Dec;4(12):867-71. doi: 10.1046/j.1365-3156.1999.00496.x.
PMID: 10632996
citation: Poland JD, Calisher CH, Monath TP, Downs WG, Murphy K. Persistence of neutralizing antibody 30-35 years after immunization with 17D yellow fever vaccine. Bull World Health Organ. 1981;59(6):895-900.
PMID: 6978196
responsible party type: Principal Investigator
investigator affiliation: Oswaldo Cruz Foundation
investigator full name: Olindo de Assis Martins Filho
investigator title: PhD
mesh term: Yellow Fever
mesh term: Fever