Mechanisms of Impaired HIV-associated B Cell and Pneumococcal Vaccine Responses
试验速览
- 阶段
- 不适用
- 入组人数
- 60
- 试验地点
- 6
- 主要终点
- B and T cell subsets
研究概览
简要总结
Human Immunodeficiency Virus (HIV) infection is complicated by high rates of infections and cancers which are often the cause of death rather than the HIV/acquired immune deficiency syndrome (AIDS) virus itself. Treatment of HIV with antiretroviral medications has decreased the frequency of many complications by over 90%, but bacterial pneumonia remains extremely high. Current vaccines are not very effective in preventing these infections in patients with HIV infection. The investigators are studying the cells (B cells) that make antibodies to fight infection by binding to and killing bacteria. The goal is to understand how HIV impairs the ability of B cells to make antibodies in sufficient quantity and of sufficient quality to protect patients with HIV to learn how to enhance protection against these infections. The investigators also seek to understand the role of the bacteria (specifically Streptococcus pneumoniae) that normally live in the nose and throat in the development of pneumonia and other infections.
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
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •For HIV-infected subjects:
- •adults aged 18-55 years
- •>200 CD4+ T-cells/microliter
- •no antiretroviral therapy (at the time of nasal swab/week 0)
- •receiving antiretroviral therapy for >6 weeks (at the time of vaccination/week 12)
- •For HIV-seronegative controls:
- •adults aged 18-55 years
排除标准
- •For all subjects:
- •age <18 or >55 years
- •history of prior pneumococcal vaccination
- •immunosuppressive therapy, defined as: prednisone >15mg/day currently or >14 days in the past 3 months, cytotoxic agents, anti-metabolites, cyclosporine, anti-tumor necrosis factor, B cell monoclonal antibodies
- •current or chronic pulmonary infection (bacterial, fungal, mycobacterial), pneumonia, or rhinosinusitis within 2 months
- •chronic lung disease
- •renal insufficiency, defined as serum creatinine >1.6
- •active liver disease, including hepatitis C virus infection
- •history of splenectomy
- •history of antibacterial therapy within 3 months of nasal swab (week 0)
- •current alcohol abuse
- •chronic heart disease
- •current cigarette smoking
结局指标
主要结局
B and T cell subsets
时间窗: Weeks -12, 0, 1, 8, 9, 16
Activation and subset distribution of B and T cell subsets and cluster of differentiation positive (CD4+) T cells and T follicular helper (TFH) cells on days 0 and 7 after stimulation
Antibody-secreting cells
时间窗: Weeks 0, 1, 8, 9
Total IgG, IgM and IgA antibody-secreting cells (ASC) enumerated by enzyme-linked immunospot (ELISPOT) on day 0 and day 7
Total IgG, IgM and IgA
时间窗: Weeks -12, 0, 1, 8, 9, 16
Total immunoglobulin G (IgG), immunoglobulin M (IgM) and immunoglobulin A (IgA) produced from culture of peripheral blood mononuclear cells (PBMC) stimulated in triplicate with B cell stimuli on day 7 by enzyme-linked immunosorbent assay (ELISA)
AID and BCL-6 production
时间窗: Weeks -12, 0, 1, 8, 9, 16
RNA extraction for activation-induced cytidine deaminase (AID) and B cell lymphoma protein 6 (BCL6) expression and mutation from stimulated B cells
次要结局
- S.pneumoniae colonization and nasopharyngeal microbiome(Weeks -12, 0, 8, 16)
- S.pneumoniae urine antigen positivity(Week -12)