Exploratory Study Into Age-related Immunological Differences Related to Immunogenicity in Influenza Vaccination and Herpes Zoster Vaccination
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 148
- 试验地点
- 1
- 主要终点
- Changes in cytokine productions of PBMCs upon incubation with viral, bacterial, and fungal antigens
研究概览
简要总结
Vaccines are used to prevent infectious diseases worldwide. Unfortunately, many vaccines, like the flu vaccine, are less effective in older adults.
This single-centre open label partially randomised, partially placebo-controlled trial evaluates the differences in immune response between young and older adults after vaccination with a quadrivalent inactivated influenza vaccine and an adjuvanted herpes zoster vaccination.
Exploring the underlying mechanisms between the differences in immunogenicity can provide important information for future vaccine development.
详细描述
Rationale: Vaccination of the older adults is often advised as they are a high-risk population; however, vaccine efficacy generally decreases with age. This is mainly due to a decrease in adaptive immune responses known as immunosenescence, which is a factor influencing the response to influenza vaccination. On the other hand, there are vaccines that show high efficacy (more than 95%) in older adults, one of the most effective being the AS01 adjuvanted herpes zoster vaccine, Shingrix. The differential immune pathways associated with vaccine responsiveness as well as the immune mechanisms by which adjuvants overcome immunosenescence remain poorly understood. Targeting key immune pathways could be a way to improve vaccine efficacy in older adults.
Objective
To explore immunological features between young and older adults after administration of an adjuvanted herpes zoster (Shingrix) or influenza unadjuvanted (Fluarix) vaccine that could explain differences in vaccine immunogenicity.
Study design: A single centre open label, randomised, and partially placebo-controlled trial Study population: Approximately 140 healthy adults, 80 of which are between 18-35 years old, the other 60 are 60+ years old.
Intervention: Two groups of young and elderly volunteers receive recombinant zoster vaccine (Shingrix), while two other groups will receive a quadrivalent influenza vaccine (Fluarix). Two groups of young volunteers will receive a placebo.
Main study parameter: To identify immune senescence-related differences contributing to vaccine immunogenicity
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Age between 18-35 years old OR age ≥60 years old
- •Written informed consent
排除标准
- •Known allergy to (components of) the influenza or herpes zoster vaccine
- •Immunocompromised subjects and subjects with active malignancy within the last two years
- •Previous herpes zoster vaccination in the last year
- •Receipt of any vaccination 4 weeks prior to the start of the study or plans to receive any other vaccination in the first 2 months after inclusion
- •Use of systemic immunomodulatory drugs:steroids, anti-inflammatory biological treatments (e.g. anti-cytokine monoclonal antibodies)
- •Acute or active illness within two weeks prior to the start of the study
- •Pregnant, breastfeeding or planning to become pregnant during the study period
研究组 & 干预措施
1: Young adults herpes zoster vaccination
Young adults between 18 and 35 years old will receive the herpes zoster vaccine (Shingrix). 60 days later, they will receive a booster dose.
干预措施: Herpes zoster vaccination (Shingrix, GSK) (Biological)
2: Older adults herpes zoster vaccination
Adults older than 60 years of age will receive the herpes zoster vaccine (Shingrix). 60 days later, they will receive a booster dose.
干预措施: Herpes zoster vaccination (Shingrix, GSK) (Biological)
3: Young adults influenza vaccination
Young adults between 18 and 35 years old will receive the influenza vaccine (Fluarix Tetra).
干预措施: Influenza Vaccine (Fluarix Tetra Northern Hemisphere 2021 or 2022, GSK) (Biological)
4: Older adults influenza vaccination
Adults older than 60 years of age will receive the influenza vaccine (Fluarix Tetra).
干预措施: Influenza Vaccine (Fluarix Tetra Northern Hemisphere 2021 or 2022, GSK) (Biological)
5: Young adults herpes zoster vaccination related placebo
Young adults between 18 and 35 years old will receive the placebo injection (0.9% NaCl). 60 days later, they will receive another placebo.
干预措施: Placebo (Biological)
6: Young adults influenza vaccination related placebo
Young adults between 18 and 35 years old will receive the placebo injection (0.9% NaCl).
干预措施: Placebo (Biological)
结局指标
主要结局
Changes in cytokine productions of PBMCs upon incubation with viral, bacterial, and fungal antigens
时间窗: 6 months after the second dose of herpes zoster vaccination
IL-6, TNF, IL-1b, IFNg cytokine concentrations will be measured.
Change in transcriptional profile of individual cells from PBMC population
时间窗: 6 months after influenza vaccination
Gene expression profile of PBMCs will be measured by single cell-RNA sequencing.
Transcriptional profile of individual cells from PBMC population
时间窗: 6 months after the second dose of herpes zoster vaccination
Gene expression profile of PBMCs will be measured by single cell-RNA sequencing.
Changes in cytokine productions of PBMCs upon incubation with viral, bacterial, and fungal antigens
时间窗: 2 months after influenza vaccination
IL-6, TNF, IL-1b, IFNg cytokine concentrations will be measured.
Changes in cytokine productions of PBMCs upon incubation with viral, bacterial, and fungal antigens
时间窗: 6 months after influenza vaccination
IL-6, TNF, IL-1b, IFNg cytokine concentrations will be measured.
Changes in cytokine productions of PBMCs upon incubation with viral, bacterial, and fungal antigens
时间窗: 2 months after the first dose of herpes zoster vaccination
IL-6, TNF, IL-1b, IFNg cytokine concentrations will be measured.
Changes in cytokine productions of PBMCs upon incubation with viral, bacterial, and fungal antigens
时间窗: 2 months after the second dose of herpes zoster vaccination
IL-6, TNF, IL-1b, IFNg cytokine concentrations will be measured.
Change in transcriptional profile of individual cells from PBMC population
时间窗: 2 months after influenza vaccination
Gene expression profile of PBMCs will be measured by single cell-RNA sequencing.
Transcriptional profile of individual cells from PBMC population
时间窗: 2 months after the first dose of herpes zoster vaccination
Gene expression profile of PBMCs will be measured by single cell-RNA sequencing.
Transcriptional profile of individual cells from PBMC population
时间窗: 2 months after the second dose of herpes zoster vaccination
Gene expression profile of PBMCs will be measured by single cell-RNA sequencing.
次要结局
- Shingles vaccine-specific antibody production in the serum(2 months after the first herpes zoster vaccination)
- Changes in the adaptive immune cell populations in blood(6 months after the second dose of herpes zoster vaccination)
- Baseline DNA methylation(Baseline (before vaccination))
- Changes in B and T cell receptor repertoires(2 months after the second dose of herpes zoster vaccination)
- Changes in circulating protein concentrations(2 months after the second dose of herpes zoster vaccination)
- Changes in epigenetic markers in PBMCs(6 months after the second herpes zoster vaccination)
- C-reactive protein in the serum(Baseline (before vaccination))
- Influenza vaccine-specific antibodies in the serum(2 months after influenza vaccination)
- Shingles vaccine-specific antibody production in serum(2 months after the second herpes zoster vaccination)
- Percentage of participants reporting local reactions(7 days after influenza and herpes zoster vaccination)
- Percentage of participants reporting systemic events(7 days after influenza and herpes zoster vaccination)
- Changes in the adaptive immune cell populations in blood(2 months after influenza vaccination)
- Changes in the adaptive immune cell populations in blood(6 months after influenza vaccination)
- Changes in the adaptive immune cell populations in blood(2 months after the first dose of herpes zoster vaccination)
- Changes in the adaptive immune cell populations in blood(2 months after the second dose of herpes zoster vaccination)
- Changes in B and T cell receptor repertoires(2 months after influenza vaccination)
- Changes in B and T cell receptor repertoires(2 months after the first dose of herpes zoster vaccination)
- Changes in circulating protein concentrations(2 months after influenza vaccination)
- Changes in circulating protein concentrations(2 months after the first dose of herpes zoster vaccination)
- Changes in epigenetic markers in PBMCs(2 months after influenza vaccination)
- Changes in epigenetic markers in PBMCs(6 months after influenza vaccination)
- Changes in epigenetic markers in PBMCs(2 months after the first herpes zoster vaccination)
- Changes in epigenetic markers in PBMCs(2 months after the second herpes zoster vaccination)