Pneumonia Vaccine in Aging HIV Positive Individuals
Condition: Pneumococcal Infection
MeSH terms: Pneumococcal Infections
Study type: Interventional
Phase: Early Phase 1

Summary: 
      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.
    

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.

        3. 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:

        1. Receive the FDA approved PCV13 and PPV23

        2. 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.

        3. 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.
    

Intervention name(s): 23-valent pneumococcal polysaccharide vaccine; 13-valent pneumococcal conjugate vaccine
Intervention type(s): Biological; Biological
Intervention description(s): One standard adult dose of the 23-valent pneumococcal polysaccharide 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 intervention name(s): PPV23 or Pneumovax; PCV13 or Prevnar 13
Intervention MeSH terms: Vaccines; Heptavalent Pneumococcal Conjugate Vaccine
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: pneumococcal conjugate vaccine; aging HIV