Immune Response to Pneumococcal Vaccination in HIV Infected Individuals
Condition: Pneumococcal Infection
MeSH terms: Pneumococcal Infections
Study type: Interventional
Phase: Early Phase 1

Summary: 
      The purpose of the study. To characterize the immune response to the pneumococcal vaccine in
      HIV positive individuals and to dissect the most appropriate timing and frequency of
      vaccination.
    

Detailed description: 
      All potential study candidates will be asked to fill out a questionnaire concerning their
      medical history and medications. This survey will determine eligibility. If eligible, as part
      of the experimental protocol the HIV positive participants will agree to be randomized to
      immediate vs. delayed pneumococcal immunization and 3 blood draws around the time of
      immunization. The HIV negative control population will agree to immunization with
      pneumococcal polysaccharide vaccine (PPV), not standard of care for this population, and 3
      blood draws around the time of immunization. The investigators will study the effect of
      pneumococcal vaccination in HIV positive adults. At the present time it is recommended that
      all HIV positive individuals receive the pneumococcal vaccine at the time of diagnosis with
      those with cluster of differentiation (CD4) count <200 to be vaccinated either immediately or
      alternatively, treated with highly active antiretroviral therapy (HAART) for 6 months
      followed by PPV. All patients are recommended to be re-vaccinated at 5 years. This is the
      standard of care. It is however unclear how the HIV positive patients respond to PPV. In the
      1st part of the study, Part I, newly diagnosed HIV positive individuals will be recruited. As
      standard of care, these individuals will receive the pneumococcal vaccine regardless of their
      participation in this study. Those that agree to participate in the study will be grouped
      according to their CD4 count: >500, 200-500 or <200. Those with a CD4 count <200 will be
      randomly assigned to receive the vaccine immediately or to receive HAART for 6 months prior
      to vaccination, this is in accordance with the present recommendations, either immediate
      vaccination or giving HAART for 6 months prior to vaccination is considered acceptable.. Thus
      ALL HIV positive individuals will receive the vaccine as presently recommended. The HIV
      positive volunteers agree to (experimental part of the protocol):

        1. Be randomized to either immediate vaccination vs. 6 months after start of HAART if the
           CD4 count is <200

        2. Donate blood specimens at 3 different times: day 0, day of vaccination: 2 mL, at day 7,
           40 mL and at day 28-42 a one time sample of 2 mL.

        3. Have their blood samples subjected to antibody analysis (concentration and functional
           activity) and antibody gene usage analysis There will be 4 HIV positive groups in this
           part of the study: CD4>500, CD4 200-500, CD4 < 200 immediate vaccination and CD4 <200,
           delayed vaccination.

      There will be 19 individuals per group. The HIV negative controls in Part I of the study
      (n=19) who agree to participate will also be vaccinated with the pneumococcal vaccine. This
      is NOT a vaccine recommended for healthy adults but is NOT contra-indicated.

      Thus as part of the experimental procedure for these individuals they will:

        1. Receive the FDA approved pneumococcal vaccine

        2. Blood samples will be obtained at day 0: 2 mL, day 7 40 mL and day 28-42, one time
           sample of 2 mL.

        3. Blood samples will be analyzed for antibody concentration, functional activity and gene
           family usage.

      In summary, we will study a total of 5 groups in Part I:

      Group 1: HIV positive CD4>500 Group 2: HIV positive CD4 200-500 Group 3: HIV positive CD4 <
      200 immediate vaccination Group 4: HIV positive CD4<200 delayed (6 months) vaccination Group
      5: HIV negative In part II of the study the investigators will evaluate the effect of a
      second pneumococcal vaccination, which is presently recommended, in HIV positive individuals,
      to be received 5 years after the first vaccination. Again, only those HIV positive
      individuals who are due for their second pneumovax will be asked to participate. They will be
      grouped according to their CD4 counts as CD4 >500 or CD4 200-500. Thus ALL HIV positive
      individuals will receive the vaccine as recommended.

      The HIV positive volunteers solely agree to;

        1. Donate blood specimens at 3 different occasions: day 0, day of vaccination: 2 mL, at day
           7, 40 mL and at day 28-42 a one time sample of 2 mL.

        2. Have their blood samples subjected to antibody analysis (concentration and functional
           activity) and antibody gene usage analysis There will be 2 HIV positive groups: CD4>500
           and CD4 count 200-500. There will be 19 individuals per group.

      The HIV negative controls in Part II of the study who agree to participate will be recruited
      from the population of individuals previously vaccinated with pneumovax. They will also be
      vaccinated for the second time with the pneumococcal vaccine, 5 years after the first
      vaccination. This is NOT a vaccine recommended for healthy adults but is NOT
      contra-indicated. Thus as part of the experimental procedure for these individuals they will:

        1. Receive the FDA approved pneumococcal vaccine

        2. Blood samples will be obtained at day 0: 2 mL, day 7 40 mL and day 28-42 one time sample
           of 2 mL.

        3. Blood samples will be analyzed for antibody concentration, functional activity and gene
           family usage.

      In summary, we will study 3 groups in Part II of the study Group 6: HIV positive CD4>500, 2nd
      PPV Group 7: HIV positive CD4 200-500, 2nd PPV Group 8: HIV negative, 2nd PPV.
    

Intervention name(s): PPV23
Intervention type(s): Biological
Intervention description(s): 23 valent pneumococcal polysaccharide vaccine in Healthy adults.
Other intervention name(s): 23 valent pneumococcal polysaccharide vaccine
Intervention MeSH terms: Heptavalent Pneumococcal Conjugate Vaccine
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention