Immune Response to Toll-Like Receptor 9-Agonist Adjuvanted Pneumococcal Vaccination in HIV Infected Adults
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 97
- 试验地点
- 2
- 主要终点
- Numbers of vaccine high responders - defined as 2-fold increase and IgG levels ≥1 µg/mL to at least 5 of 7 pneumococcal serotypes (by quantitative IgG measurements) - in the CpG 7909 group vs. the control group
研究概览
简要总结
The purpose of this study is to determine whether TLR-9 adjuvanted pneumococcal is more immunogenic than pneumococcal vaccination alone in HIV-infected adults.
详细描述
Pneumococcal disease is a major source of morbidity and mortality in HIV-patients. HIV-patients are vaccine hyporesponders. A good immune response to pneumococcal vaccination enhances vaccine effectiveness, thereby preventing the morbidity and mortality caused by pneumococcal disease. Even when an optimized regimen containing both conjugated and polysaccharide pneumococcal vaccine is used, only 13% of the immunized HIV patients are high responders at week 96. Recent data indicate that TLR9-agonists have excellent vaccine adjuvant potential and are safe to use in immunocompetent as well as immunocompromised individuals. The aim of this study is to evaluate the qualitative and quantitive immune response to pneumococcal vaccination with or without TLR9-agonist in HIV-infected adults
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Written informed consent and authority statement provided according to local regulatory and ethical practice using a participant information sheet and informed consent form approved by the responsible Ethics Committee.
- •HIV-seropositive individuals.
排除标准
- •Pregnancy as determined by a positive urine beta-hCG (if female)
- •Participant unwilling to use reliable contraception methods for the duration of the trial. Reliable methods of birth control include: pharmacologic contraceptives including oral, parenteral, and transcutaneous delivery; condoms with spermicide; diaphragm with spermicide; surgical sterilization; vaginal ring; intrauterine device; abstinence; and post-menopause (if female)
- •Currently breast-feeding (if female)
- •Latest CD4 count < 200 x106 cells/µL
- •Viral load (HIV RNA) > 50 copies/mL if on HAART (defined as at least three antiretrovirals including either a protease inhibitor or a NNRTI, i.e. combivir 300/150 mg x2 + stocrin 600 mg x1 for a minimum of 6 months)
- •Previous enrollment in this study
- •Any medical, psychiatric, social, or occupational condition or other responsibility that, in the judgment of the Principal Investigator (PI), would interfere with the evaluation of study objectives (such as severe alcohol abuse, severe drug abuse, dementia)
- •Unable to follow protocol regimen
- •Pneumococcal vaccination 5 years or less prior to inclusion
- •Planned participation in other vaccination trials during the time of the study
结局指标
主要结局
Numbers of vaccine high responders - defined as 2-fold increase and IgG levels ≥1 µg/mL to at least 5 of 7 pneumococcal serotypes (by quantitative IgG measurements) - in the CpG 7909 group vs. the control group
时间窗: At day 270
次要结局
- Functional activity of anticapsular antibodies measured by OPA(At day 90, 120, 270, 300)
- Safety/Tolerability(During the entire trial period)
- Nasopharyngeal pneumococcal colonization(At day 270)
- Predictors of antibody response, i.e. CD4+ cell count and sCD163(At baseline)
- Numbers of vaccine high responders - defined as 2-fold increase and IgG levels ≥1 µg/mL to at least 5 of 7 pneumococcal serotypes (by quantitative IgG measurements) - in the CpG 7909 group vs. the control group(At day 90,120 and 300)
- Quantity and differentiation of IgG subtypes for HAART-experienced and HAART-naive individuals(Day 0, 90, 120)
- Cytokine response to various antigens by in vitro cell stimulation for HAART-experienced and HAART-naive individuals(At day 0, 90, 120)