Immune response to pneumococcal vaccination in aging HIV positive adults.

老年艾滋病毒阳性成年人对肺炎球菌疫苗接种的免疫反应。

• 批准号: 8716638
• 负责人: M.A. Julia WESTERINK
• 金额: $ 31.48万
• 依托单位: UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-15 至 2018-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8716638
• 关键词: Adjuvant; Adult; Affect; Age-Years; Aging; Antibodies; Antibody Formation; Antigens; B-Lymphocytes; BLR1 gene; Bacterial Pneumonia; Binding; Biological Assay; Blood specimen; CD19 gene; CD4 Positive T Lymphocytes; CXCL13 gene; Carrier Proteins; Cell Proliferation; Childhood; Chronic; Clinical; Conjugate Vaccines; Data; Development; Diphtheria; Disease; Elderly; Enzyme-Linked Immunosorbent Assay; Epitopes; Future; Goals; HIV; HIV Seropositivity; Helper-Inducer T-Lymphocyte; Highly Active Antiretroviral Therapy; IL2 gene; Immune; Immune response; Immunity; Immunization; Immunoglobulin G; Immunoglobulin M; Incidence; Individual; Inflammation; Interferon Type II; Interleukin-10; Ionomycin; Knowledge; Label; Life Expectancy; MS4A1 gene; Manuscripts; Measures; Memory B-Lymphocyte; Methods; Multivariate Analysis; Nature; Participant; Patients; Persons; Phenotype; Pneumococcal conjugate vaccine; Pneumococcal vaccine; Pneumonia; Polysaccharides; Polyvalent pneumococcal vaccine; Population; Preparation; Production; Recommendation; Regimen; Research; Secondary to; Staining method; Stains; Streptococcus pneumoniae; T cell response; T-Lymphocyte; T-Lymphocyte Subsets; TI 2 Antigens; Testing; Vaccination; Vaccines; Vulnerable Populations; Work; base; cross reacting material 197; cytokine; efficacy trial; high risk; humoral immunity deficiency; immunosenescence; improved; inflammatory marker; interleukin-21; novel; older patient; peripheral blood; public health relevance; response; young adult

DESCRIPTION: Streptococcus pneumonia is the most common cause of bacterial pneumonia in HIV+ individuals. Despite routine pneumococcal polysaccharide vaccination (PPV23) and the widespread use of HAART, antibody levels and the functional activity of antibodies are lower than in HIV-negative persons and disease incidence therefore remains 35-50 fold higher than in HIV negative individuals. Similarly, PPV23 is less effective in the elderly. The introduction of HAART has led to a significant increase in life-expectancy of HIV+ persons and soon more than 50% of HIV positive individuals will be older than 50. This population will likely be at very high risk for IPD based on their immune deficiencies secondary to HIV AND immunosenescence as suggested using multivariate analysis. Although there is considerable overlap in B cell alterations caused by HIV and by aging we have recently found that aging and HIV result in distinct B cell deficiencies. The recommendations for pneumococcal vaccination in HIV+ persons have recently changed to include the 13-valent conjugate vaccine (PCV13). Although several studies show short-term efficacy or increased antibody response in HIV+ persons with PCV13, others do not, in either HIV+ population or in elderly. Large efficacy trials necessary to establish clinical superiority of PCV13 compared to PPV23 will likely not be conducted, particularly in the aging HIV+ population. It is therefore essential that we define immune responses to conjugated and free- polysaccharide preparations by examining traditional antibody and functional levels and at B and T cell levels, critically affected by aging and HIV, both characterized by chronic inflammation. The fundamental question posed in this proposal is: will PCV followed by PPV23 elicit an immune response compatible with improved protection or is it identical to the immune response following PPV23, known to be associated with suboptimal protection? Aim 1 test the hypothesis that vaccination with either PPV23 alone or a PCV13 containing regimen results in comparable antibody levels/functional activity, determined by levels of chronic inflammation. In aim 2, we test the hypothesis that the levels and phenotype of PPS-specific B cells will be comparable between the PPV23 and PCV13/PPV23 recipients. Phenotype analysis using a variety of B cell markers will be used to characterize PPS-labeled B cells. Specific phenotypes will be correlated with antibody levels, OPA and inflammatory markers and compared to historic populations immunized with PPV23. In aim 3 we will test the hypothesis that functional T cell helper responses to the conjugate vaccine will predict levels of switched B cells and IgG produced after vaccination. This work is important and novel because it examines antigen-specific responses post immunization to the number one cause of pneumonia in HIV and elderly patients. It is high impact as it will determine if either of the present vaccines is acceptable methods of inducing protective immunity or new methods with different adjuvants are required.

描述：肺炎链球菌是HIV+个体中细菌性肺炎的最常见原因。尽管常规的肺炎球菌多糖疫苗接种（PPV23）和广泛使用HAART，但抗体水平和抗体的功能活性低于HIV阴性人和疾病的发病率，因此仍比HIV负个体高35-50倍。同样，PPV23在老年人中的有效性较低。 HAART的引入导致HIV+患者的生命预期生命显着增加，不久，超过50％的HIV阳性个体将大于50岁。基于其继发于HIV的免疫缺陷和使用多变量分析建议的IPD的IPD风险很高。尽管由HIV引起的B细胞改变存在相当大的重叠，并且我们最近发现衰老和HIV导致了不同的B细胞缺陷。 HIV+患者中肺炎球菌疫苗接种的建议最近已更改为包括13个价值结合疫苗（PCV13）。尽管几项研究表明，艾滋病毒+ PCV13患者的短期疗效或抗体反应增加，但在HIV+人群中或老年人中均不存在。与PPV23相比，建立PCV13的临床优势所需的大型疗效试验可能不会进行，尤其是在衰老的HIV+种群中。因此，至关重要的是，我们必须通过检查传统抗体和功能水平以及在B和T细胞水平下定义对共轭和自由糖糖制剂的免疫反应，受到衰老和HIV的严重影响，均以慢性炎症为特征。该提案中提出的基本问题是：PCV之后是PPV23引起的免疫反应与改善的保护兼容，还是与PPV23后的免疫反应相同，已知与次优保护有关？ AIM 1检验以下假设：单独使用PPV23的疫苗接种或含有方案的PCV13导致可比抗体水平/功能活性，这是由慢性炎症水平决定的。 在AIM 2中，我们检验了以下假设：PPS特异性B细胞的水平和表型将在PPV23和PCV13/PPV23受体之间相当。使用各种B细胞标记物的表型分析将用于表征PPS标记的B细胞。特定的表型将与抗体水平，OPA和炎症标志物相关，并将其与PPV23免疫的历史种群相比。在AIM 3中，我们将检验以下假设：功能性T细胞辅助器对结合疫苗的反应将预测疫苗接种后产生的开关B细胞和IgG水平。这项工作很重要且新颖，因为它检查了对艾滋病毒和老年患者肺炎的第一原因后的抗原特异性反应。它具有很高的影响，因为它将确定当前的疫苗是否是诱导保护性免疫的可接受方法，或者需要具有不同佐剂的新方法。