Clinical Trials

MainTitle

Pneumonia Vaccine in Aging HIV Positive Individuals

This study has been completed
Sponsor
University of Toledo Health Science Campus

Collaborator
National Institute on Aging (NIA)

Information provided by (Responsible Party)
University of Toledo Health Science Campus
ClinicalTrials.gov Identifier
NCT02558751

First received: September 16, 2015
Last updated: September 23, 2015
Last Verified: September 2015
History of Changes
Purpose

Purpose

The investigators hypothesized that vaccination with either the 23-valent pneumococcal polysaccharide vaccine (PPV23) alone or the 13-valent pneumococcal conjugate vaccine (PCV 13) followed by PPV23 results in similar antibody levels/functional activity and induce a similar pneumococcal polysaccharide (PPS)-specific B cell response in HIV-positive individuals >50 years of age and HIV-negative persons>50 years of age. The investigators immunized the study group HIV+ persons>50 and controls (HIV negative >50 years) with PCV13 followed by PPV23 and HIV+>50 with PPV23 alone. The investigators examined immune responses to PPS23F and PPS14 on a quantitative and qualitative level using ELISA and opsonophagocytic assays (OPA).

To test the hypothesis that the levels of antigen specific B cells identified with PPS were comparable between the PPV23 and PCV13 vaccine recipients. 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 historic populations immunized with PPV.

Condition Intervention Phase
Pneumococcal Infection

Biological : 23-valent pneumococcal polysaccharide vaccine
Biological : 13-valent pneumococcal conjugate vaccine
Early Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Immune Response to Pneumococcal Vaccination in Aging HIV Positive Individuals

Further study details as provided by University of Toledo Health Science Campus:

Primary Outcome Measures

  • Antibody response measured by ELISA (ug/ml) [ Time Frame: Change in ug/ml from day 0 to day 30 ]
  • Opsonophagocytic antibody activity measured by opsonophagocytic assay (OPA titer) [ Time Frame: Change in OPA titer from day 0 to day 30 ]
  • Antibody response measured by ELISA (ug/ml) [ Time Frame: Change in ug/ml from day 0 to day 90 ]
  • Opsonophagocytic antibody activity measured by opsonophagocytic assay (OPA titer) [ Time Frame: Change in OPA titer from day 0 to day 90 ]
Secondary Outcome Measures:
  • B cell phenotype of PPS-specific B cells expressing CD27+IgM+: flowcytometry (%) [ Time Frame: Change from day 0 to day 7 in % ]
  • Serum C-reactive protein (ng/ml) [ Time Frame: day 0 ]
  • Flow cytometry : percentage cells expressing BAFF-R on surface (%) [ Time Frame: Change from day 0 to day 7 ]
  • Flow cytometry : percentage cells expressing BAFF-R on surface (%) [ Time Frame: Change from day 56 to day 63 ]
  • B cell phenotype of PPS-specific B cells expressing CD27IgM: flowcytometry (%) [ Time Frame: Change from day 56 to day 63 (%) ]
  • Serum IL-6 level (pg/ml) [ Time Frame: Day 0 ]
  • Serum sCD27 (U/ml) [ Time Frame: Day 0 ]
  • Serum sCD30 (U/ml) [ Time Frame: Day 0 ]
  • Serum BAFF concentration (pg/ml) [ Time Frame: Day 0 ]
  • Serum TACI concentration (pg/ml) [ Time Frame: Day 0 ]
  • Serum BCMA concentration (pg/ml) [ Time Frame: Day 0 ]
  • Flow cytometry : percentage cells expressing CD40 on surface (%) [ Time Frame: Change from day 0 to day 7 (%) ]
  • Flow cytometry : percentage cells expressing CD40 on surface (%) [ Time Frame: Change from day 56 to day 63 (%) ]
  • Flow cytometry : percentage cells expressing CD21 on surface (%) [ Time Frame: Change from day 0 to day 7 (%) ]
  • Flow cytometry : percentage cells expressing CD21 on surface (%) [ Time Frame: Change from day 56 to day 63 (%) ]
  • Flow cytometry : percentage cells expressing TACI on surface (%) [ Time Frame: Change from day 0 to day 7 (%) ]
  • Flow cytometry : percentage cells expressing TACI on surface (%) [ Time Frame: Change from day 56 to day 63 (%) ]

Enrollment: 51
Study Start Date: July 2013
Study Completion Date: June 2015
Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
Active Comparator: HIV positive PPV23
HIV-positive individuals 50-65 years of age immunized with one dose of the 23-valent pneumococcal polysaccharide vaccine, PPV23
Biological: 23-valent pneumococcal polysaccharide vaccine

One standard adult dose of the 23-valent pneumococcal polysaccharide vaccine

Other Name: PPV23 or Pneumovax
Active Comparator: HIV positive PCV13/PPV23
HIV-positive individual 50-65 years of age, Intervention: one dose of 13-valent pneumococcal conjugate vaccine,PCV13, followed 8 weeks later with one dose of 23-valent pneumococcal polysaccharide vaccine, PPV23
Biological: 23-valent pneumococcal polysaccharide vaccine

One standard adult dose of the 23-valent pneumococcal polysaccharide vaccine

Other Name: PPV23 or Pneumovax
Biological: 13-valent pneumococcal conjugate vaccine

One dose of the 13-valent pneumococcal conjugate vaccine, PCV13, followed 8 weeks later by one dose of the 23-valent pneumococcal polysaccharide vaccine, PPV23.

Other Name: PCV13 or Prevnar 13
Active Comparator: HIV negative PCV13/PPV23
HIV-negative individual 50-65 years of age, Intervention: one dose of 13-valent pneumococcal conjugate vaccine,PCV13, followed 8 weeks later with one dose of 23-valent pneumococcal polysaccharide vaccine, PPV23
Biological: 23-valent pneumococcal polysaccharide vaccine

One standard adult dose of the 23-valent pneumococcal polysaccharide vaccine

Other Name: PPV23 or Pneumovax
Biological: 13-valent pneumococcal conjugate vaccine

One dose of the 13-valent pneumococcal conjugate vaccine, PCV13, followed 8 weeks later by one dose of the 23-valent pneumococcal polysaccharide vaccine, PPV23.

Other Name: PCV13 or Prevnar 13

Detailed Description:

All potential study candidates were asked to fill out a questionnaire concerning their medical history and medications. This survey determined eligibility. If eligible, as part of the experimental protocol the HIV positive participants agreed to be randomized to PPV23 alone versus PCV13 followed 8 weeks later by PPV23 immunization and 3 to 5 blood draws around the time of immunization. The HIV negative control population agreed to immunization with PCV13 followed 8 weeks later by PPV23, not standard of care for this population, and 5 blood draws around the time of immunization. The investigators compared the effect of single dose pneumococcal polysaccharide vaccination versus PCV13 followed by PPV23 vaccination in HIV positive adults. Prior to 2012, the standard of care of HIV positive adults included vaccination with PPV23. In 2012, these recommendations changed and it was recommended that all HIV positive adults be vaccinated with PCV13 followed at least 8 weeks later by PPV23. The benefit of this vaccination protocol over PPV23 alone in HIV positive adults >50 years of age however had not been studied. As part of this study, all HIV positive adults>50 years of age and a CD4 count>200 who were due for pneumococcal vaccination as standard of care, were asked to participate in the study. Those who agreed and were eligible to participate were randomly assigned to receive PCV13 followed at least 8 weeks later with PPV23 or received a single vaccination with PPV23. As standard of care, all individuals who were due for their pneumococcal vaccine and were not eligible for the study received PCV13 followed by PPV23.
The HIV positive volunteers (n=37) agreed to (experimental part of the protocol):

  1. Be randomized to either vaccination with PCV13 followed by PPV23 OR PPV23 alone.
  2. Donate blood specimens at 3-5 different times:

PPV23 group:day 0, day of vaccination: 2 mL, at day 7, 40 mL and at day 28-42 a one time sample of 2 mL PCV13/PPV23 group: day 0, day of vaccination with PCV13: 2 mL, at day 7, 40 mL and at day 56, day of PPPV23, 2 mL, day 63 a 40 mL sample and finally at day 90 a one time sample of 2 mL.
  • Have blood samples subjected to antibody analysis (concentration and functional activity) and PPS-specific B cell phenotype and tumor necrosis factor receptors (TNFR) .

  • The HIV negative controls in the study (n=14) who agree to participate were vaccinated with the PCV13 followed by PPV23.This is NOT a vaccine regime recommended for healthy adults but is NOT contraindicated.
    Thus as part of the experimental procedure for these individuals they will:
  • Receive the FDA approved PCV13 and PPV23
  • Blood samples were obtained at day 0, day of vaccination with PCV13: 2 mL, at day 7, 40 mL and at day 56, day of PPPV23, 2 mL, day 63 a 40 mL sample and finally at day 90 a one time sample of 2 mL.
  • Blood samples were analyzed for antibody concentration, functional activity and PPS-specific B cell phenotype and TNFR.

  • In summary,the investigators studied 3 populations, all were between 50-65 years of age:
    Group 1: HIV positive CD4>200 vaccinated with PPV23 Group 2: HIV positive CD4> 200 vaccinated with PCV13 followed 8 weeks later by PPV23 Group 3: HIV negative vaccinated with PCV13/PPV23.

    Eligibility

    Eligibility

    Ages Eligible for Study: 50 Years to 65 Years  
    Sexes Eligible for Study: All  
    Accepts Healthy Volunteers: Yes  

    Criteria

    Inclusion Criteria:

    • HIV negative:
    • never immunized with PCV13
    • HIV positive:
    • need for pneumococcal vaccination per standard of care


    Exclusion Criteria:
    • steroid use
    • other immunosuppressive agents;
    • pregnancy
    • incapable of completing consent form

    contacts and locations

    Contacts and Locations

    Choosing to participate in a study is an important personal decision.Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.For general information, see Learn About Clinical Studies.

    Please refer to this study by its ClinicalTrials.gov identifier: NCT02558751

    Locations

    United States, Ohio
    The University of Toledo-Health Science Campus
    Toledo, Ohio, United States, 43614

    Sponsors and Collaborators

    University of Toledo Health Science Campus
    National Institute on Aging (NIA)

    Investigators

    Principal Investigator: Maria AJ Westerink, M.D. University of Toledo
    More Information

    More Information


    Responsible Party: University of Toledo Health Science Campus  
    ClinicalTrials.gov Identifier: NCT02558751   History of Changes  
    Other Study ID Numbers: R01AG045973  
      R01AG045973  
    Study First Received: September 16, 2015  
    Last Updated: September 23, 2015  

    Keywords provided by University of Toledo Health Science Campus:

    pneumococcal conjugate vaccine
    aging HIV

    Additional relevant MeSH terms:
    Pneumococcal Infections
    Vaccines
    Heptavalent Pneumococcal Conjugate Vaccine

    ClinicalTrials.gov processed this data on December 15, 2017
    This information is provided by ClinicalTrials.gov.