Immune Response to Pneumococcal Vaccination in Aging HIV Positive Individuals
试验速览
- 阶段
- 早期 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 51
- 试验地点
- 2
- 主要终点
- Antibody response measured by ELISA (ug/ml)
研究概览
简要总结
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.
详细描述
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):
- Be randomized to either vaccination with PCV13 followed by PPV23 OR PPV23 alone.
- 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 50 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •HIV negative:
- •never immunized with PCV13
- •HIV positive:
- •need for pneumococcal vaccination per standard of care
排除标准
- •steroid use
- •other immunosuppressive agents;
- •pregnancy
- •incapable of completing consent form
结局指标
主要结局
Antibody response measured by ELISA (ug/ml)
时间窗: Change in ug/ml from day 0 to day 90
Opsonophagocytic antibody activity measured by opsonophagocytic assay (OPA titer)
时间窗: Change in OPA titer from day 0 to day 90
次要结局
- Serum BAFF concentration (pg/ml)(Day 0)
- Serum C-reactive protein (ng/ml)(day 0)
- Flow cytometry : percentage cells expressing BAFF-R on surface (%)(Change from day 56 to day 63)
- Serum sCD30 (U/ml)(Day 0)
- Serum TACI concentration (pg/ml)(Day 0)
- Flow cytometry : percentage cells expressing CD40 on surface (%)(Change from day 56 to day 63 (%))
- Flow cytometry : percentage cells expressing TACI on surface (%)(Change from day 56 to day 63 (%))
- B cell phenotype of PPS-specific B cells expressing CD27+IgM+: flowcytometry (%)(Change from day 0 to day 7 in %)
- B cell phenotype of PPS-specific B cells expressing CD27IgM: flowcytometry (%)(Change from day 56 to day 63 (%))
- Serum IL-6 level (pg/ml)(Day 0)
- Serum sCD27 (U/ml)(Day 0)
- Serum BCMA concentration (pg/ml)(Day 0)
- Flow cytometry : percentage cells expressing CD21 on surface (%)(Change from day 56 to day 63 (%))