Immune Response to Pneumococcal Vaccination in Aging Renal Transplant Recipients
试验速览
- 阶段
- 早期 1 期
- 状态
- 终止
- 入组人数
- 57
- 试验地点
- 2
- 主要终点
- Percentage of Polysaccharide Specific B Cells (% Cells/mL)
研究概览
简要总结
The goal of the research proposed in the current application is to first define how much antibody aging renal transplant and dialysis recipients make after they are vaccinated with the pneumonia vaccine and how this compares to similar aged persons with good renal function and healthy young adults. The investigators will study differences in the kind of B cells and markers on the B cells that are known to be important in the response to the pneumonia vaccine in aging renal transplant and aging dialysis recipients compared to similarly aged and young healthy controls. Finally, the investigators will study how safe the pneumonia vaccine is in aging renal transplants. The answers to these questions will help in designing a better vaccine for older people with a renal transplant or on dialysis.
详细描述
Objectives / Specific Aims
Individuals >65 years of age, are the most rapidly growing population amongst those with end stage renal disease (ESRD) and account for more than 18% of renal transplant (RT) recipients.
The incidence of pneumococcal disease is significantly higher in both elderly and those with RT and the combination of these factors is likely additive, if not synergistic, for invasive pneumococcal disease (IPD). It is recommended that both elderly>65 and RT recipients be vaccinated with a regimen that includes both the 13-valent pneumococcal conjugate vaccine (PCV13) and the 23-valent pneumococcal polysaccharide vaccine (PPV23). However, small immunogenicity studies performed in the transplant populations have not shown superiority of a PCV containing regimen. Moreover, the addition of PCV to the pneumococcal vaccine regimen does not improve protective immunity in this population. Studies to date fail to elucidate the possible foundation of the disappointing immune responses to the PCV regimens.
Specific Aim 1. The investigators will define immune responses by measuring serum antibody and functional antibody responses to PPS 14, 19A and 23F following PCV13 vaccination in RT recipients 65-75 years of age and compare these to: RT recipients 35-45 years of age and persons with DM/HTN but normal function 65-75 years of age to dissect out the age and RT components respectively. Healthy persons 35-45 and 65-75 years of age will be studied as age appropriate reference.
Specific Aim 2. The investigators will measure and characterize the antigen-specific B cell subset response following immunization with PCV13 in the RT recipients 65-75 years of age and compare them to each of the groups described in Specific Aim 1 using flow cytometry and fluorescently labeled PPS and monoclonal antibodies. These measures will be correlated with post-immunization functional antibody activity, a surrogate of protection.
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
- None
入排标准
- 年龄范围
- 35 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Inclusion criteria are group specific. HBV, HCV and HIV testing are not necessary in the RT groups as all RT recipients are tested prior to transplant. The investigators will not restrict volunteers with respect to gender, ethnic or racial group.
- •Groups 1 (65-75 yrs) and 2 (35-45 yrs) Renal Transplant populations
- •End stage renal disease cause either DM2 and/or hypertension (HTN)
- •Renal transplant >12 months ago
- •Group 3: Diabetic/hypertensive 65-75 year old controls
- •With DM2 and/or HTN
- •Previous immunization with PPV23 >1 year prior
- •Willingness to be tested for HIV, HBV and HCV
- •"normal kidney function" defined as glomerular filtration rate (GFR) of 60% or above
- •Group 4: Healthy Control 65-75 yr old
- •Without DM2
- •May have high blood pressure (systolic>140 and/or diastolic>90) as long as it is well controlled (systolic<140 and/or diastolic <90) and has not affected kidney function.
- •Previous receipt of PPV23 > 1 year prior
- •Willingness to be tested for HIV, HBV and HCV
- •Group 5: Healthy Control 35-45 yr old
- •Without DM
- •May have high blood pressure (systolic>140 and/or diastolic>90) as long as it is well controlled (systolic<140 and/or diastolic <90) and has not affected kidney function.
- •Willingness to be tested for HIV, HBV and HCV and filling out a medical questionnaire that will include diabetes screening.
排除标准
- •Exclusion criteria are either applicable to all groups or group specific. Therefore we have listed the exclusion criteria applicable to ALL groups first. Group specific criteria are listed under each group.
- •Exclusion Criteria common to all groups
- •Previous immunization with PCV
- •Pregnancy, no contraceptive practice in women of childbearing age, or breastfeeding
- •Known anaphylaxis, hypersensitivity or "bad allergic reaction" to the pneumonia vaccine. This does not include egg allergy or previous Guillan Barre syndrome.
- •Those who received blood products or gamma globulin within 3 months.
- •Inability to comprehend or sign the informed consent form
- •Previous/present illness that may affect immune response to the vaccine
- •previous pneumococcal disease
- •removal of the spleen
- •auto-immune disease such as lupus or rheumatoid arthritis
- •end-stage liver disease
- •Significant abnormalities (3xULN and all those considered to be critical values) in CBC, chemistries including glucose.
- •HIV, HBsAg or HCV positivity
- •Receipt of PPV23 within 1 year
- •Groups 1 (65-75 yrs) and 2 (35-45 yrs) Renal Transplant populations
- •Medications that are known to affect immune function (chemotherapy, anti-TNF agents) with the exception of anti-rejection medication.
- •Episode of acute rejection within the last 6 month period
- •Group 3: Diabetic/hypertensive 65-75 year old controls
- •Medications that are known to affect immune function (chemotherapy, anti-TNF agents).
- •The inclusion/exclusion criteria will be determined by chart review.
- •Group 4: Healthy Control 65-75 yr old
- •Medications that are known to affect immune function (chemotherapy, anti-TNF agents).
- •The inclusion/exclusion criteria will be determined by chart review and pregnancy test for females of child bearing potential.
- •Group 5: Healthy Control 35-45 yr old
- •Medications that are known to affect immune function (chemotherapy, anti-TNF agents).
- •The inclusion/exclusion criteria will be determined by chart review and pregnancy test for females of child bearing potential.
研究组 & 干预措施
1.Aging RT
Renal transplant recipients between 65-75 years of age, on stable immunosuppression. who previously (>1 year prior) received the 23 valent pneumococcal polysaccharide vaccine (pneumovax23). Cause or renal failure was either DMII or HTN.
干预措施: Peripheral blood sample (Other)
2.Young RT
Renal transplant recipients between 35-45 years of age, on stable immunosuppression. who previously (>1 year prior) received the 23 valent pneumococcal polysaccharide vaccine (pneumovax23). Cause or renal failure was either DMII or HTN.
干预措施: Peripheral blood sample (Other)
3.Healthy elderly
Healthy persons between the ages 65-75 who previously (>1 year prior) received the 23 valent pneumococcal polysaccharide vaccine (pneumovax23)
干预措施: Peripheral blood sample (Other)
4.Elderly DMII or HTN and normal renal function
Persons between the ages 65-75 with DMII or hypertension but normal renal function who previously (>1 year prior) received the 23 valent pneumococcal polysaccharide vaccine (pneumovax23)
干预措施: Peripheral blood sample (Other)
5.Healthy young
Healthy persons between the ages 35-45 who previously (>1 year prior) received the 23 valent pneumococcal polysaccharide vaccine (pneumovax23) or are willing to receive PPV23 and 1 year later Prevnar 13.
干预措施: 23 valent pneumococcal polysaccharide vaccine (Drug)
5.Healthy young
Healthy persons between the ages 35-45 who previously (>1 year prior) received the 23 valent pneumococcal polysaccharide vaccine (pneumovax23) or are willing to receive PPV23 and 1 year later Prevnar 13.
干预措施: 13 valent conjugated pneumococcal vaccine (Biological)
5.Healthy young
Healthy persons between the ages 35-45 who previously (>1 year prior) received the 23 valent pneumococcal polysaccharide vaccine (pneumovax23) or are willing to receive PPV23 and 1 year later Prevnar 13.
干预措施: Peripheral blood sample (Other)
结局指标
主要结局
Percentage of Polysaccharide Specific B Cells (% Cells/mL)
时间窗: day 7
percentage of polysaccharide specific B cells, and percentage of IgM memory B cells/mL in % cells/mL induced by vaccination with PCV13
Anti-pneumococcal IgG Antibody (ug/ml) Change
时间窗: Baseline, 30 days
Measure the opsonic antibody response against streptococcus pneumonia serotypes 14, 19A and 23F at days 0 and 30. Comparing elderly RT recipients versus healthy elderly and elderly with DM/HTN.
Opsonophagocytic Antibody Titer Serum Dilution Difference Between Healthy Elderly, Elderly With DM/HTN and Elderly With RT.
时间窗: Baseline and 30 days
Measure the serum opsonophagocytic activity against streptococcus pneumonia serotypes 14, 19A and 23F on days 0 and 30 by opsonophagocytic assay.
次要结局
- Inflammatory Markers Serum Levels Pre-immunization(Day 0 pre-immunization)