<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/NCT03039491</url>
  </required_header>
  <id_info>
    <org_study_id>MUSC vaccine study</org_study_id>
    <nct_id>NCT03039491</nct_id>
  </id_info>
  <brief_title>Immune Response to Pneumococcal Vaccination in Aging HIV Positive Adults</brief_title>
  <official_title>Immune Response to Pneumococcal Vaccination in Aging HIV Positive Individuals</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Medical University of South Carolina</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Medical University of South Carolina</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The investigators hypothesized that pneumococcal vaccination with either the 23-valent&#xD;
      pneumococcal polysaccharide vaccine PPV-23 (Pneumovax-23) alone or the 13-valent pneumococcal&#xD;
      conjugate vaccine PCV-13 (Prevnar-13) followed by PPV-23 results in a similar antibody&#xD;
      levels/functional antibody activity and induce similar pneumococcal polysaccharide&#xD;
      (PPS)-specific B cell response in HIV positive individuals &gt; 50 years of age, HIV positive&#xD;
      individuals 21-40 years of age as compared to HIV negative &gt; 50 years of age. The&#xD;
      investigators immunized the study groups HIV+ persons &gt;50, HIV+ persons 21-40 and controls&#xD;
      (HIV negative) with PCV 13 followed by PPV23 and HIV&gt;50 with PPV alone and examined immune&#xD;
      responses to polysaccharide (PPS) 23 (F),14, 3, 7 (F) and 19 (A) using polysaccharide&#xD;
      specific ELISA and opsonophagocytic assays (OPA). Pre- and post-immunization peripheral blood&#xD;
      samples were obtained. Extensive B cell phenotype analysis using fluorescent antibodies was&#xD;
      used to characterize PPS-labeled B cells. Specific phenotypes were correlated with antibody&#xD;
      levels and OPA and compared to populations immunized with PPV&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The purpose of this study is to learn more about how older people with HIV respond to the&#xD;
      pneumococcal or pneumonia vaccine. Pneumonia occurs very frequently in in older persons AND&#xD;
      in persons who are infected with HIV. Therefore, it is common practice to vaccinate against&#xD;
      pneumonia in these patient populations. Because older patients with HIV fit both of these&#xD;
      categories, it is believed that they are at an increased risk of pneumonia.&#xD;
&#xD;
      There are two types of pneumonia vaccines available for adults approved by the Federal Drug&#xD;
      Administration (FDA). One is called the pneumococcal polysaccharide vaccine (PPV23) and&#xD;
      protects against 23 different strains of the pneumonia bacteria. The other type of vaccine&#xD;
      called the pneumococcal conjugate vaccine (PCV13) protects against different strains of the&#xD;
      pneumonia bacteria.&#xD;
&#xD;
      Until 2012, it was recommended that all HIV-positive adults receive PPV23 when diagnosed with&#xD;
      HIV and again 5 years later. More recently, the guidelines have changed to all HIV-positive&#xD;
      adults are to receive PCV13, followed later with PPV23. At this point in time, it is not&#xD;
      clear which regimen works better in aging HIV positive adults. Investigators are doing this&#xD;
      study to compare the effectiveness of each vaccine regimen in aging HIV positive adults&#xD;
      compared to healthy adults. Although several studies show short-term efficacy or increased&#xD;
      antibody response in HIV+ persons with this vaccine, others do not, in either HIV+ population&#xD;
      or in elderly. Large efficacy trials necessary to establish clinical superiority of PCV&#xD;
      compared to PPV will likely not be conducted, particularly in the aging HIV+ population. It&#xD;
      is therefore essential to define immune responses to conjugated and free-polysaccharide&#xD;
      preparations by examining traditional antibody and functional levels as well as B cell&#xD;
      subsets, critically affected by aging and HIV. Will either PCV or PPV elicit an immune&#xD;
      response compatible with protection in this population? Based on persistent B cell&#xD;
      perturbations in HAART-treated persons, it is hypothesized that immunization of aging HIV+&#xD;
      persons with PPV23 will be as effective as a PCV13 containing regimen on a quantitative,&#xD;
      qualitative, B and T cell level and that the magnitude of this response will be related to&#xD;
      the degree of chronic inflammation. The proposed studies are highly significant as they will&#xD;
      define the B and T cell responses to a TI-2 and T-cell dependent form of pneumococcal vaccine&#xD;
      in the aging HIV+ population. These data will provide the necessary basis for development of&#xD;
      a rational vaccination approach, including the potential use of novel adjuvant. In this study&#xD;
      the investigators will:&#xD;
&#xD;
        1. Test the hypothesis that vaccination with either PPV alone (TI-2) or a PCV containing&#xD;
           regimen (TD) results in similar antibody levels/functional activity, that are determined&#xD;
           by levels of chronic inflammation in aging HIV+. The investigators will immunize the&#xD;
           study group HIV+ persons 50-65 and controls (HIV+21-40 and HIV- 50-65 years) with PCV13&#xD;
           followed by PPV23 and HIV+ 50-65 and HIV- 50-65 with PPV alone. The investigators will&#xD;
           examine immune responses to pneumococcal polysaccharides (PPS) 23 (F), 14, 3, 7 (F) and&#xD;
           19 (A) on a quantitative and qualitative level using ELISA and opsonophagocytic assays&#xD;
           (OPA) and correlate the response to the degree of inflammation measured in each&#xD;
           participant.&#xD;
&#xD;
        2. To test the hypothesis that the levels of antigen specific B cells identified with PPS&#xD;
           will be comparable between the PPV and PCV vaccine recipients. Pre- and&#xD;
           post-immunization peripheral blood samples will be obtained. Extensive phenotype&#xD;
           analysis using antibodies against cluster of differentiation (CD)19, 20, 21, 27, 38, 40,&#xD;
           immunoglobulin M (IgM) , B-cell activating factor (BAFF), trans-membrane activator and&#xD;
           calcium modulator and cyclophilin ligand interactor (TACI), and B-cell maturation&#xD;
           antigen (BCMA) markers will be used to characterize PPS-labeled B cells. Specific&#xD;
           phenotypes will be correlated with antibody levels, OPA and inflammatory markers and&#xD;
           compared to the control populations immunized with PPV.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 1, 2015</start_date>
  <completion_date type="Actual">March 30, 2020</completion_date>
  <primary_completion_date type="Actual">March 30, 2020</primary_completion_date>
  <phase>Early Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Antibody response</measure>
    <time_frame>Change in ug/mL from day 0 to 30 days after receipt of PPV23</time_frame>
    <description>Measure antibody response by ELISA (ug/mL)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>opsonophagocytic antibody activity</measure>
    <time_frame>Change in opsonophagocytic titer from day 0 to 30 days after receipt of PPV23</time_frame>
    <description>opsonophagocytic antibody response measured by opsonophagocytic assay (OPA)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>PPS-specific B cell phenotype</measure>
    <time_frame>Change from day 0 to day 7 post-vaccination</time_frame>
    <description>Measure: B cell phenotype of PPS-specific B cells expressing CD27+IgM+: flowcytometry (%)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PPS-specific B cell phenotype</measure>
    <time_frame>Change from day 56 to day 63 post-vaccination</time_frame>
    <description>Measure: B cell phenotype of PPS-specific B cells expressing CD27+IgM+: flowcytometry (%)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Expression of TACI on PPS-specific B cells</measure>
    <time_frame>change from day 0 to day 7</time_frame>
    <description>Measure:Flow cytometry: percentage of PPS-specific B cells expressing TACI on their surface (%)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Expression of TACI on PPS-specific B cells</measure>
    <time_frame>change from day 56 to day 63</time_frame>
    <description>Measure:Flow cytometry: percentage of PPS-specific B cells expressing TACI on their surface (%)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Expression of BAFFR on PPS-specific B cells</measure>
    <time_frame>change from day 0 to day 7</time_frame>
    <description>Measure:Flow cytometry: percentage of PPS-specific B cells expressing BAFFR on their surface (%)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Expression of BAFFR on PPS-specific B cells</measure>
    <time_frame>change from day 56 to day 63</time_frame>
    <description>Measure:Flow cytometry: percentage of PPS-specific B cells expressing BAFFR on their surface (%)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Expression of BCMA on PPS-specific B cells</measure>
    <time_frame>change from day 0 to day 7</time_frame>
    <description>Measure:Flow cytometry: percentage of PPS-specific B cells expressing BAFFR on their surface (%)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Expression of BCMA on PPS-specific B cells</measure>
    <time_frame>change from day 7 to day 63</time_frame>
    <description>Measure:Flow cytometry: percentage of PPS-specific B cells expressing BAFFR on their surface (%)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Expression of CD40 on PPS-specific B cells</measure>
    <time_frame>change from day 0 to day 7</time_frame>
    <description>Measure:Flow cytometry: percentage of PPS-specific B cells expressing CD40 on their surface (%)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Expression of CD40 on PPS-specific B cells</measure>
    <time_frame>change from day 56 to day 63</time_frame>
    <description>Measure:Flow cytometry: percentage of PPS-specific B cells expressing CD40 on their surface (%)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Expression of cluster of differentiation 21 (CD21) on PPS-specific B cells</measure>
    <time_frame>change from day 0 to day 7</time_frame>
    <description>Measure:Flow cytometry: percentage of PPS-specific B cells expressing CD21 on their surface (%)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Expression of CD21 on PPS-specific B cells</measure>
    <time_frame>change from day 56 to day 63</time_frame>
    <description>Measure:Flow cytometry: percentage of PPS-specific B cells expressing CD21 on their surface (%)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum interleukin-6 (IL-6)</measure>
    <time_frame>Day 0</time_frame>
    <description>Measure serum levels IL-6</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum BAFF</measure>
    <time_frame>Day 0</time_frame>
    <description>Measure serum levels BAFF</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum APRIL</measure>
    <time_frame>Day 0</time_frame>
    <description>Measure serum levels APRIL</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum IL-10</measure>
    <time_frame>Day 0</time_frame>
    <description>Measure serum levels IL-10</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum IL-1(RA)</measure>
    <time_frame>Day 0</time_frame>
    <description>Measure serum levels IL-1RA</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum IL-1(B)</measure>
    <time_frame>Day 0</time_frame>
    <description>Measure serum levels IL-1B</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum IL-8</measure>
    <time_frame>Day 0</time_frame>
    <description>Measure serum levels IL-8</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum TNFalpha</measure>
    <time_frame>Day 0</time_frame>
    <description>Measure serum levels TNFalpha</description>
  </secondary_outcome>
  <number_of_arms>8</number_of_arms>
  <enrollment type="Actual">160</enrollment>
  <condition>HIV Lipodystrophy</condition>
  <condition>Aging</condition>
  <arm_group>
    <arm_group_label>HIV+ 50-65, CD4&gt;200 PCV/PPV</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>HIV+ individuals , 50-65 years of age with a nadir cluster of differentiation (CD) 4 count &gt;200 to receive PCV13 vaccine followed 8 weeks later by PPV23&#xD;
Intervention: 13 valent Pneumococcal conjugate vaccine (PCV13) followed 8 weeks later by 23 valent pneumococcal polysaccharide vaccine</description>
  </arm_group>
  <arm_group>
    <arm_group_label>HIV+ 50-65, CD4&lt;200 PCV/PPV</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>HIV+ individuals , 50-65 years of age with a nadir CD4 count &lt;200 to receive PCV13 vaccine followed 8 weeks later by PPV23&#xD;
Intervention: 13 valent Pneumococcal conjugate vaccine (PCV13) followed 8 weeks later by 23 valent pneumococcal polysaccharide vaccine</description>
  </arm_group>
  <arm_group>
    <arm_group_label>HIV+ 50-65, CD4&gt;200 PPV</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>HIV+ individuals , 50-65 years of age with a nadir CD4 count &gt;200 to receive PPV23 only&#xD;
Intervention: 23 valent pneumococcal polysaccharide vaccine only</description>
  </arm_group>
  <arm_group>
    <arm_group_label>HIV+ 50-65, CD4&lt;200 PCV</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>HIV+ individuals , 50-65 years of age with a nadir CD4 count &lt;200 to receive PPV23 only&#xD;
Intervention: 23 valent pneumococcal polysaccharide vaccine only</description>
  </arm_group>
  <arm_group>
    <arm_group_label>HIV- 50-65, PCV/PPV</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>HIV- individuals , 50-65 years of age immunized with PCV13 followed by PPV23&#xD;
Intervention: 13 valent Pneumococcal conjugate vaccine (PCV13) followed 8 weeks later by 23 valent pneumococcal polysaccharide vaccine</description>
  </arm_group>
  <arm_group>
    <arm_group_label>HIV- 50-65, PPV</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>HIV- individuals, 50-65 years of age immunized with PPV23 only.&#xD;
Intervention: 23 valent pneumococcal polysaccharide vaccine only</description>
  </arm_group>
  <arm_group>
    <arm_group_label>HIV+ 21-40, CD4&gt;200 PCV/PPV</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>HIV+ individuals , 21-40 years of age with a nadir CD4 count &gt;200 to receive PCV13 vaccine followed 8 weeks later by PPV23&#xD;
Intervention: 13 valent Pneumococcal conjugate vaccine (PCV13) followed 8 weeks later by 23 valent pneumococcal polysaccharide vaccine</description>
  </arm_group>
  <arm_group>
    <arm_group_label>HIV+ 21-40, CD4&lt;200 PCV/PPV</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>HIV+ individuals , 21-40 years of age with a nadir CD4 count &lt;200 to receive PCV13 vaccine followed 8 weeks later by PPV23&#xD;
Intervention: 13 valent Pneumococcal conjugate vaccine (PCV13) followed 8 weeks later by 23 valent pneumococcal polysaccharide vaccine</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Pneumococcal polysaccharide vaccine 23 valent</intervention_name>
    <description>This is the pneumococcal vaccine consisting of the capsular polysaccharides of 23 serotypes of Streptococcus pneumoniae</description>
    <arm_group_label>HIV+ 21-40, CD4&lt;200 PCV/PPV</arm_group_label>
    <arm_group_label>HIV+ 21-40, CD4&gt;200 PCV/PPV</arm_group_label>
    <arm_group_label>HIV+ 50-65, CD4&lt;200 PCV</arm_group_label>
    <arm_group_label>HIV+ 50-65, CD4&lt;200 PCV/PPV</arm_group_label>
    <arm_group_label>HIV+ 50-65, CD4&gt;200 PCV/PPV</arm_group_label>
    <arm_group_label>HIV+ 50-65, CD4&gt;200 PPV</arm_group_label>
    <arm_group_label>HIV- 50-65, PCV/PPV</arm_group_label>
    <arm_group_label>HIV- 50-65, PPV</arm_group_label>
    <other_name>Pneumovax</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>13 valent conjugated pneumococcal vaccine</intervention_name>
    <description>This is the pneumococcal vaccine consisting of the capsular polysaccharides of 13 serotypes of Streptococcus pneumoniae conjugated to non-toxic diphtheria carrier protein 197</description>
    <arm_group_label>HIV+ 21-40, CD4&lt;200 PCV/PPV</arm_group_label>
    <arm_group_label>HIV+ 21-40, CD4&gt;200 PCV/PPV</arm_group_label>
    <arm_group_label>HIV+ 50-65, CD4&lt;200 PCV/PPV</arm_group_label>
    <arm_group_label>HIV+ 50-65, CD4&gt;200 PCV/PPV</arm_group_label>
    <arm_group_label>HIV- 50-65, PCV/PPV</arm_group_label>
    <other_name>Prevnar 13</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:HIV+ 21-40 years of age HIV+ 50-65 years of age HIV- 50-65 years of age&#xD;
&#xD;
        -&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Previous immunization with pneumococcal vaccine less than 5 years ago&#xD;
&#xD;
          -  pregnancy and absence of contraceptive practice in women of childbearing age and&#xD;
             breast feeding&#xD;
&#xD;
          -  known anaphylaxis, hypersensitivity to the pneumonia vaccine&#xD;
&#xD;
          -  those who received blood products or gammaglobulin in last 3 months&#xD;
&#xD;
          -  inability to comprehend or sihn informed consent&#xD;
&#xD;
          -  Medications known to affect immune function (chemotherapy, an&#xD;
             angiotensin-converting-enzyme (ACE) inhibitors, corticosteroids, anti-TNFalpha agents)&#xD;
&#xD;
          -  previous disease/present illness that may affect response to vaccination: previous&#xD;
             pneumococcal disease, removal of spleen, auto-immune disease, end stage renal disease&#xD;
             (ESRD) or end stage liver disease, cancer)&#xD;
&#xD;
          -  significant (3x upper limit of normal) in complete blood count (CBC), chemistries,&#xD;
             immunoglobulin levels&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <gender_based>Yes</gender_based>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Maria A. Julia Westerink, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Medical University of South Carolina</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Medical University of South Carolina</name>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <zip>29425</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Crum-Cianflone NF, Huppler Hullsiek K, Roediger M, Ganesan A, Patel S, Landrum ML, Weintrob A, Agan BK, Medina S, Rahkola J, Hale BR, Janoff EN; Infectious Disease Clinical Research Program HIV Working Group. A randomized clinical trial comparing revaccination with pneumococcal conjugate vaccine to polysaccharide vaccine among HIV-infected adults. J Infect Dis. 2010 Oct 1;202(7):1114-25. doi: 10.1086/656147.</citation>
    <PMID>20795819</PMID>
  </reference>
  <reference>
    <citation>de Roux A, Schmole-Thoma B, Siber GR, Hackell JG, Kuhnke A, Ahlers N, Baker SA, Razmpour A, Emini EA, Fernsten PD, Gruber WC, Lockhart S, Burkhardt O, Welte T, Lode HM. Comparison of pneumococcal conjugate polysaccharide and free polysaccharide vaccines in elderly adults: conjugate vaccine elicits improved antibacterial immune responses and immunological memory. Clin Infect Dis. 2008 Apr 1;46(7):1015-23. doi: 10.1086/529142. Erratum In: Clin Infect Dis. 2008 May 1;46(9):1488. Schmoele-Thoma, B [corrected to Schmole-Thoma, B].</citation>
    <PMID>18444818</PMID>
  </reference>
  <reference>
    <citation>French N, Gordon SB, Mwalukomo T, White SA, Mwafulirwa G, Longwe H, Mwaiponya M, Zijlstra EE, Molyneux ME, Gilks CF. A trial of a 7-valent pneumococcal conjugate vaccine in HIV-infected adults. N Engl J Med. 2010 Mar 4;362(9):812-22. doi: 10.1056/NEJMoa0903029.</citation>
    <PMID>20200385</PMID>
  </reference>
  <reference>
    <citation>Baxendale HE, Keating SM, Johnson M, Southern J, Miller E, Goldblatt D. The early kinetics of circulating pneumococcal-specific memory B cells following pneumococcal conjugate and plain polysaccharide vaccines in the elderly. Vaccine. 2010 Jul 5;28(30):4763-70. doi: 10.1016/j.vaccine.2010.04.103. Epub 2010 May 14.</citation>
    <PMID>20471437</PMID>
  </reference>
  <reference>
    <citation>Penaranda M, Payeras A, Cambra A, Mila J, Riera M; Majorcan Pneumococcal Study Group. Conjugate and polysaccharide pneumococcal vaccines do not improve initial response of the polysaccharide vaccine in HIV-infected adults. AIDS. 2010 May 15;24(8):1226-8. doi: 10.1097/QAD.0b013e3283389de5.</citation>
    <PMID>20299956</PMID>
  </reference>
  <reference>
    <citation>Khaskhely N, Mosakowski J, Thompson RS, Khuder S, Smithson SL, Westerink MA. Phenotypic analysis of pneumococcal polysaccharide-specific B cells. J Immunol. 2012 Mar 1;188(5):2455-63. doi: 10.4049/jimmunol.1102809. Epub 2012 Jan 23.</citation>
    <PMID>22271652</PMID>
  </reference>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>January 30, 2017</study_first_submitted>
  <study_first_submitted_qc>January 30, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">February 1, 2017</study_first_posted>
  <last_update_submitted>June 12, 2020</last_update_submitted>
  <last_update_submitted_qc>June 12, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 16, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>pneumococcal vaccination</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lipodystrophy</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vaccines</mesh_term>
    <mesh_term>Heptavalent Pneumococcal Conjugate Vaccine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>The data will be made available once analysis is completed through publications in peer reviewed journals.</ipd_description>
  </patient_data>
  <!-- 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/NCT03039491
org study id: MUSC vaccine study
nct id: NCT03039491
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
The investigators hypothesized that pneumococcal vaccination with either the 23-valent
      pneumococcal polysaccharide vaccine PPV-23 (Pneumovax-23) alone or the 13-valent pneumococcal
      conjugate vaccine PCV-13 (Prevnar-13) followed by PPV-23 results in a similar antibody
      levels/functional antibody activity and induce similar pneumococcal polysaccharide
      (PPS)-specific B cell response in HIV positive individuals > 50 years of age, HIV positive
      individuals 21-40 years of age as compared to HIV negative > 50 years of age. The
      investigators immunized the study groups HIV+ persons >50, HIV+ persons 21-40 and controls
      (HIV negative) with PCV 13 followed by PPV23 and HIV>50 with PPV alone and examined immune
      responses to polysaccharide (PPS) 23 (F),14, 3, 7 (F) and 19 (A) using polysaccharide
      specific ELISA and opsonophagocytic assays (OPA). Pre- and post-immunization peripheral blood
      samples were obtained. Extensive B cell phenotype analysis using fluorescent antibodies was
      used to characterize PPS-labeled B cells. Specific phenotypes were correlated with antibody
      levels and OPA and compared to populations immunized with PPV
The purpose of this study is to learn more about how older people with HIV respond to the
      pneumococcal or pneumonia vaccine. Pneumonia occurs very frequently in in older persons AND
      in persons who are infected with HIV. Therefore, it is common practice to vaccinate against
      pneumonia in these patient populations. Because older patients with HIV fit both of these
      categories, it is believed that they are at an increased risk of pneumonia.

      There are two types of pneumonia vaccines available for adults approved by the Federal Drug
      Administration (FDA). One is called the pneumococcal polysaccharide vaccine (PPV23) and
      protects against 23 different strains of the pneumonia bacteria. The other type of vaccine
      called the pneumococcal conjugate vaccine (PCV13) protects against different strains of the
      pneumonia bacteria.

      Until 2012, it was recommended that all HIV-positive adults receive PPV23 when diagnosed with
      HIV and again 5 years later. More recently, the guidelines have changed to all HIV-positive
      adults are to receive PCV13, followed later with PPV23. At this point in time, it is not
      clear which regimen works better in aging HIV positive adults. Investigators are doing this
      study to compare the effectiveness of each vaccine regimen in aging HIV positive adults
      compared to healthy adults. Although several studies show short-term efficacy or increased
      antibody response in HIV+ persons with this vaccine, others do not, in either HIV+ population
      or in elderly. Large efficacy trials necessary to establish clinical superiority of PCV
      compared to PPV will likely not be conducted, particularly in the aging HIV+ population. It
      is therefore essential to define immune responses to conjugated and free-polysaccharide
      preparations by examining traditional antibody and functional levels as well as B cell
      subsets, critically affected by aging and HIV. Will either PCV or PPV elicit an immune
      response compatible with protection in this population? Based on persistent B cell
      perturbations in HAART-treated persons, it is hypothesized that immunization of aging HIV+
      persons with PPV23 will be as effective as a PCV13 containing regimen on a quantitative,
      qualitative, B and T cell level and that the magnitude of this response will be related to
      the degree of chronic inflammation. The proposed studies are highly significant as they will
      define the B and T cell responses to a TI-2 and T-cell dependent form of pneumococcal vaccine
      in the aging HIV+ population. These data will provide the necessary basis for development of
      a rational vaccination approach, including the potential use of novel adjuvant. In this study
      the investigators will:

        1. Test the hypothesis that vaccination with either PPV alone (TI-2) or a PCV containing
           regimen (TD) results in similar antibody levels/functional activity, that are determined
           by levels of chronic inflammation in aging HIV+. The investigators will immunize the
           study group HIV+ persons 50-65 and controls (HIV+21-40 and HIV- 50-65 years) with PCV13
           followed by PPV23 and HIV+ 50-65 and HIV- 50-65 with PPV alone. The investigators will
           examine immune responses to pneumococcal polysaccharides (PPS) 23 (F), 14, 3, 7 (F) and
           19 (A) on a quantitative and qualitative level using ELISA and opsonophagocytic assays
           (OPA) and correlate the response to the degree of inflammation measured in each
           participant.

        2. To test the hypothesis that the levels of antigen specific B cells identified with PPS
           will be comparable between the PPV and PCV vaccine recipients. Pre- and
           post-immunization peripheral blood samples will be obtained. Extensive phenotype
           analysis using antibodies against cluster of differentiation (CD)19, 20, 21, 27, 38, 40,
           immunoglobulin M (IgM) , B-cell activating factor (BAFF), trans-membrane activator and
           calcium modulator and cyclophilin ligand interactor (TACI), and B-cell maturation
           antigen (BCMA) markers will be used to characterize PPS-labeled B cells. Specific
           phenotypes will be correlated with antibody levels, OPA and inflammatory markers and
           compared to the control populations immunized with PPV.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Antibody response
time frame: Change in ug/mL from day 0 to 30 days after receipt of PPV23
description: Measure antibody response by ELISA (ug/mL)
measure: opsonophagocytic antibody activity
time frame: Change in opsonophagocytic titer from day 0 to 30 days after receipt of PPV23
description: opsonophagocytic antibody response measured by opsonophagocytic assay (OPA)
measure: PPS-specific B cell phenotype
time frame: Change from day 0 to day 7 post-vaccination
description: Measure: B cell phenotype of PPS-specific B cells expressing CD27+IgM+: flowcytometry (%)
measure: PPS-specific B cell phenotype
time frame: Change from day 56 to day 63 post-vaccination
description: Measure: B cell phenotype of PPS-specific B cells expressing CD27+IgM+: flowcytometry (%)
measure: Expression of TACI on PPS-specific B cells
time frame: change from day 0 to day 7
description: Measure:Flow cytometry: percentage of PPS-specific B cells expressing TACI on their surface (%)
measure: Expression of TACI on PPS-specific B cells
time frame: change from day 56 to day 63
description: Measure:Flow cytometry: percentage of PPS-specific B cells expressing TACI on their surface (%)
measure: Expression of BAFFR on PPS-specific B cells
time frame: change from day 0 to day 7
description: Measure:Flow cytometry: percentage of PPS-specific B cells expressing BAFFR on their surface (%)
measure: Expression of BAFFR on PPS-specific B cells
time frame: change from day 56 to day 63
description: Measure:Flow cytometry: percentage of PPS-specific B cells expressing BAFFR on their surface (%)
measure: Expression of BCMA on PPS-specific B cells
time frame: change from day 0 to day 7
description: Measure:Flow cytometry: percentage of PPS-specific B cells expressing BAFFR on their surface (%)
measure: Expression of BCMA on PPS-specific B cells
time frame: change from day 7 to day 63
description: Measure:Flow cytometry: percentage of PPS-specific B cells expressing BAFFR on their surface (%)
measure: Expression of CD40 on PPS-specific B cells
time frame: change from day 0 to day 7
description: Measure:Flow cytometry: percentage of PPS-specific B cells expressing CD40 on their surface (%)
measure: Expression of CD40 on PPS-specific B cells
time frame: change from day 56 to day 63
description: Measure:Flow cytometry: percentage of PPS-specific B cells expressing CD40 on their surface (%)
measure: Expression of cluster of differentiation 21 (CD21) on PPS-specific B cells
time frame: change from day 0 to day 7
description: Measure:Flow cytometry: percentage of PPS-specific B cells expressing CD21 on their surface (%)
measure: Expression of CD21 on PPS-specific B cells
time frame: change from day 56 to day 63
description: Measure:Flow cytometry: percentage of PPS-specific B cells expressing CD21 on their surface (%)
measure: Serum interleukin-6 (IL-6)
time frame: Day 0
description: Measure serum levels IL-6
measure: Serum BAFF
time frame: Day 0
description: Measure serum levels BAFF
measure: Serum APRIL
time frame: Day 0
description: Measure serum levels APRIL
measure: Serum IL-10
time frame: Day 0
description: Measure serum levels IL-10
measure: Serum IL-1(RA)
time frame: Day 0
description: Measure serum levels IL-1RA
measure: Serum IL-1(B)
time frame: Day 0
description: Measure serum levels IL-1B
measure: Serum IL-8
time frame: Day 0
description: Measure serum levels IL-8
measure: Serum TNFalpha
time frame: Day 0
description: Measure serum levels TNFalpha
arm group label: HIV+ 50-65, CD4>200 PCV/PPV
arm group type: Experimental
description: HIV+ individuals , 50-65 years of age with a nadir cluster of differentiation (CD) 4 count >200 to receive PCV13 vaccine followed 8 weeks later by PPV23
Intervention: 13 valent Pneumococcal conjugate vaccine (PCV13) followed 8 weeks later by 23 valent pneumococcal polysaccharide vaccine
arm group label: HIV+ 50-65, CD4<200 PCV/PPV
arm group type: Experimental
description: HIV+ individuals , 50-65 years of age with a nadir CD4 count <200 to receive PCV13 vaccine followed 8 weeks later by PPV23
Intervention: 13 valent Pneumococcal conjugate vaccine (PCV13) followed 8 weeks later by 23 valent pneumococcal polysaccharide vaccine
arm group label: HIV+ 50-65, CD4>200 PPV
arm group type: Experimental
description: HIV+ individuals , 50-65 years of age with a nadir CD4 count >200 to receive PPV23 only
Intervention: 23 valent pneumococcal polysaccharide vaccine only
arm group label: HIV+ 50-65, CD4<200 PCV
arm group type: Experimental
description: HIV+ individuals , 50-65 years of age with a nadir CD4 count <200 to receive PPV23 only
Intervention: 23 valent pneumococcal polysaccharide vaccine only
arm group label: HIV- 50-65, PCV/PPV
arm group type: Active Comparator
description: HIV- individuals , 50-65 years of age immunized with PCV13 followed by PPV23
Intervention: 13 valent Pneumococcal conjugate vaccine (PCV13) followed 8 weeks later by 23 valent pneumococcal polysaccharide vaccine
arm group label: HIV- 50-65, PPV
arm group type: Active Comparator
description: HIV- individuals, 50-65 years of age immunized with PPV23 only.
Intervention: 23 valent pneumococcal polysaccharide vaccine only
arm group label: HIV+ 21-40, CD4>200 PCV/PPV
arm group type: Active Comparator
description: HIV+ individuals , 21-40 years of age with a nadir CD4 count >200 to receive PCV13 vaccine followed 8 weeks later by PPV23
Intervention: 13 valent Pneumococcal conjugate vaccine (PCV13) followed 8 weeks later by 23 valent pneumococcal polysaccharide vaccine
arm group label: HIV+ 21-40, CD4<200 PCV/PPV
arm group type: Active Comparator
description: HIV+ individuals , 21-40 years of age with a nadir CD4 count <200 to receive PCV13 vaccine followed 8 weeks later by PPV23
Intervention: 13 valent Pneumococcal conjugate vaccine (PCV13) followed 8 weeks later by 23 valent pneumococcal polysaccharide vaccine
intervention type: Biological
intervention name: Pneumococcal polysaccharide vaccine 23 valent
description: This is the pneumococcal vaccine consisting of the capsular polysaccharides of 23 serotypes of Streptococcus pneumoniae
arm group label: HIV+ 21-40, CD4<200 PCV/PPV
arm group label: HIV+ 21-40, CD4>200 PCV/PPV
arm group label: HIV+ 50-65, CD4<200 PCV
arm group label: HIV+ 50-65, CD4<200 PCV/PPV
arm group label: HIV+ 50-65, CD4>200 PCV/PPV
arm group label: HIV+ 50-65, CD4>200 PPV
arm group label: HIV- 50-65, PCV/PPV
arm group label: HIV- 50-65, PPV
other name: Pneumovax
intervention type: Biological
intervention name: 13 valent conjugated pneumococcal vaccine
description: This is the pneumococcal vaccine consisting of the capsular polysaccharides of 13 serotypes of Streptococcus pneumoniae conjugated to non-toxic diphtheria carrier protein 197
arm group label: HIV+ 21-40, CD4<200 PCV/PPV
arm group label: HIV+ 21-40, CD4>200 PCV/PPV
arm group label: HIV+ 50-65, CD4<200 PCV/PPV
arm group label: HIV+ 50-65, CD4>200 PCV/PPV
arm group label: HIV- 50-65, PCV/PPV
other name: Prevnar 13
criteria: 
gender: All
gender based: Yes
minimum age: 21 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Maria A. Julia Westerink, MD
role: Principal Investigator
affiliation: Medical University of South Carolina
facility: 
country: United States
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PMID: 20795819
citation: de Roux A, Schmole-Thoma B, Siber GR, Hackell JG, Kuhnke A, Ahlers N, Baker SA, Razmpour A, Emini EA, Fernsten PD, Gruber WC, Lockhart S, Burkhardt O, Welte T, Lode HM. Comparison of pneumococcal conjugate polysaccharide and free polysaccharide vaccines in elderly adults: conjugate vaccine elicits improved antibacterial immune responses and immunological memory. Clin Infect Dis. 2008 Apr 1;46(7):1015-23. doi: 10.1086/529142. Erratum In: Clin Infect Dis. 2008 May 1;46(9):1488. Schmoele-Thoma, B [corrected to Schmole-Thoma, B].
PMID: 18444818
citation: French N, Gordon SB, Mwalukomo T, White SA, Mwafulirwa G, Longwe H, Mwaiponya M, Zijlstra EE, Molyneux ME, Gilks CF. A trial of a 7-valent pneumococcal conjugate vaccine in HIV-infected adults. N Engl J Med. 2010 Mar 4;362(9):812-22. doi: 10.1056/NEJMoa0903029.
PMID: 20200385
citation: Baxendale HE, Keating SM, Johnson M, Southern J, Miller E, Goldblatt D. The early kinetics of circulating pneumococcal-specific memory B cells following pneumococcal conjugate and plain polysaccharide vaccines in the elderly. Vaccine. 2010 Jul 5;28(30):4763-70. doi: 10.1016/j.vaccine.2010.04.103. Epub 2010 May 14.
PMID: 20471437
citation: Penaranda M, Payeras A, Cambra A, Mila J, Riera M; Majorcan Pneumococcal Study Group. Conjugate and polysaccharide pneumococcal vaccines do not improve initial response of the polysaccharide vaccine in HIV-infected adults. AIDS. 2010 May 15;24(8):1226-8. doi: 10.1097/QAD.0b013e3283389de5.
PMID: 20299956
citation: Khaskhely N, Mosakowski J, Thompson RS, Khuder S, Smithson SL, Westerink MA. Phenotypic analysis of pneumococcal polysaccharide-specific B cells. J Immunol. 2012 Mar 1;188(5):2455-63. doi: 10.4049/jimmunol.1102809. Epub 2012 Jan 23.
PMID: 22271652
responsible party type: Sponsor
mesh term: Lipodystrophy
mesh term: Vaccines
mesh term: Heptavalent Pneumococcal Conjugate Vaccine
sharing ipd: Yes
ipd description: The data will be made available once analysis is completed through publications in peer reviewed journals.