Using AS01 Adjuvant to Improve Immune Response in Older Adults Through Trained Immunity
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Host Immune Response
研究概览
简要总结
As people grow older, their immune system - the body's natural defence against diseases - becomes weaker, making them more vulnerable to infections and less responsive to vaccines. This was clearly seen during the COVID-19 pandemic, where older adults were more likely to develop severe illness. Researchers have made an interesting discovery about AS01, an ingredient already used in successful vaccines like the shingles vaccine. They found clues that AS01 might work like a general fitness trainer for the immune system, potentially making it stronger and better at fighting off various types of infections, not just specific ones. To confirm this possibility, we are conducting this research study with adults aged 21-59 to test whether AS01 by itself can boost and train the immune system, how long this boost lasts, and if it actually helps you fight off other infections more effectively.
详细描述
As people age, the immune system becomes less responsive, increasing susceptibility to infections and reducing vaccine responsiveness. AS01 is a liposome-based adjuvant used in licensed vaccines (e.g., shingles vaccine) that activates innate and adaptive immunity. Emerging evidence suggests AS01 may also induce trained immunity, a form of innate immune reprogramming that could enhance protection against unrelated infections. This study tests whether AS01 given alone can boost and train the immune system in healthy adults, how long these effects last, and whether this translates into better control of a heterologous viral challenge.
This will be a single-center, randomised, single-blind, placebo-controlled experimental medicine study at Singapore General Hospital (N=40; ages 21-59). Participants receive a single intramuscular dose of AS01 (0.5 mL) or saline placebo on Day 0. To model a controlled viral exposure, all participants then receive the licensed live-attenuated yellow fever vaccine (YF17D, Stamaril) either at 1 month (Day 30) or 3 months (Day 90) after AS01/placebo, per randomization. Serial blood sampling measures immune reprogramming, durability, and response to the viral challenge over ~2 or 4 months depending on assignment
Findings may clarify whether AS01 can be used as a standalone immune booster to rapidly enhance broad protection. Information that could be useful for outbreak preparedness, especially before pathogen-specific vaccines are available.
Therefore, (1) Early and durable innate immune changes after AS01 (e.g., gene expression and epigenetic markers in myeloid/innate cells); (2) YF17D viremia (RNAemia) after vaccination as an indicator of heterologous viral control; and (3) T-cell and B-cell responses to YF17D and how they relate to viremia, will be measured and analysed.
AS01 and YF17D are licensed components when used with their indicated vaccines. Common reactions include local injection-site symptoms and short-lived systemic symptoms; rare serious adverse events have been reported with YF17D. Participants are monitored and provided safety guidance and contact pathways throughout the study.
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
- Single (Participant)
入排标准
- 年龄范围
- 21 Years 至 59 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Adults aged 21 to 59 years of age at time of screening.
- •BMI 18.5 - 27.5 kg / m2 (BMI values for Asian population according to MOH guideline NIH Consensus Conference).
- •Satisfactory baseline medical assessment as assessed by physical examination and a stable health status. For subjects with underlying comorbidities, the conditions must be deemed stable by the investigators, and they must not have any hospitalisation relating to these conditions in the last 6 months.
- •Voluntarily participate, understand and sign an informed consent form approved by the Ethical Review Board.
- •Subjects who are willing to comply with the requirements of the study protocol and scheduled visits. These requirements include completion of the subject diary, return for follow-up visits. Subjects should also be willing to make themselves available for the duration of the study, with access to a consistent means of contact.
- •Accessible vein at the forearm for blood taking.
- •Female subjects of non-childbearing potential due to surgical sterilisation (hysterectomy or bilateral oophorectomy or tubal ligation) or menopause. Post-menopausal subjects must have had at least 12 months of natural (spontaneous) amenorrhoea.
排除标准
- •Previous vaccination against yellow fever, dengue either with a registered product or from participation in a previous vaccine study.
- •Previously received AS01-adjuvanted vaccines (e.g. Recombinant zoster vaccine, RTS,S/AS01, RSVPre-F3-AS01), either with a registered product or from participation in a previous vaccine study.
- •Planned administration of a AS01-adjuvanted vaccine or yellow fever vaccine other than the study vaccine during the study.
- •Subjects who have been unwell in the last 7 days prior to screening.
- •History of documented yellow fever and / or dengue infection.
- •Dengue seropositivity upon screening.
- •History of smoking within the last 1 year.
- •Planned travel to yellow fever endemic countries during the study.
- •Known allergy to AS01 and YF17D vaccine or their components (e.g. egg products).
- •Diagnosis of diabetes HBA1c > 6.5 according to American Diabetes Association criteria
- •Any medical condition that in the judgment of the investigator will make intramuscular injection unsafe (e.g. thrombocytopenia with platelet count < 50x10^9/L, coagulopathy, anti-coagulant therapy).
- •Risk factor for live-attenuated vaccines, including any confirmed or suspected primary or acquired immunodeficiency based on history and physical examination:
- •History of thymus gland disease
- •Haematologic neoplasms including leukaemia, lymphoma, myelodysplastic syndromes
- •Diagnosed with cancer or treatment for cancer (except for localised basal cell carcinoma) within 3 years prior to screening
- •Post-transplant: solid organ and haematopoietic stem cell transplant
- •Immunocompromised due to primary or acquired (including HIV/AIDS) immunodeficiency
- •Other significantly immunocompromising conditions
- •Administration of anti-inflammatory drugs for the past 7 days (e.g. NSAIDs, Paracetamol, aspirin).
- •Use of metformin for the last 1 month.
- •Use of corticosteroids within the last 6 months prior to the first vaccine dose (defined as prednisolone > 10 mg / day or equivalent for > 2 weeks, or prednisolone > 40mg / day or > 1 week). Inhaled and topical steroids are allowed.
- •Received biologics (such as anti-TNF inhibitors, IL-1 inhibitors, co-stimulation blockers, B-cell depleting therapy) for the last 12 months.
- •Any condition (e.g. extensive psoriasis, chronic pain syndrome, severe hearing loss, cognitive impairment, dialysis, autoimmune disorders) that in the opinion of the investigator, would complicate or compromise the study or wellbeing of the subject, or prevent completion of the study.
- •Evidence of substance abuse, or previous substance abuse.
- •Clinically significant anaemia (Hb < 10 g/dL).
- •Blood donation exceeding > 450 ml in the past 3 months.
- •Participation in a study involving administration of an investigational or non-investigational compound within the past four months or planned participation during the duration of this study.
- •Administration of any licensed vaccine within 30 days before the first study vaccine dose or planned to receive such products within 30 days after the study vaccination.
- •Received immunoglobulin or any blood products within the 90 days preceding the first dose of study vaccine or planned to receive such products during the study period.
研究组 & 干预措施
AS01 + YF17D at 1 Month
Participants receive AS01 (0.5 mL IM on Day 0) and yellow fever vaccine YF17D on Day 30.
干预措施: AS01 adjuvant (0.5 mL intramuscular) (Biological)
AS01 + YF17D at 1 Month
Participants receive AS01 (0.5 mL IM on Day 0) and yellow fever vaccine YF17D on Day 30.
干预措施: YF17D (Stamaril, Sanofi-Pasteur) (Biological)
Placebo + YF17D at 3 Months
Participants receive placebo (0.9% saline, 0.5 mL IM on Day 0) and yellow fever vaccine YF17D on Day 90.
干预措施: Placebo (NaCl 09%, 0.5mL) (Other)
AS01 + YF17D at 3 Months
Participants receive AS01 (0.5 mL IM on Day 0) and yellow fever vaccine YF17D on Day 90.
干预措施: AS01 adjuvant (0.5 mL intramuscular) (Biological)
AS01 + YF17D at 3 Months
Participants receive AS01 (0.5 mL IM on Day 0) and yellow fever vaccine YF17D on Day 90.
干预措施: YF17D (Stamaril, Sanofi-Pasteur) (Biological)
Placebo + YF17D at 1 Month
Participants receive placebo (0.9% saline, 0.5 mL IM on Day 0) and yellow fever vaccine YF17D on Day 30.
干预措施: YF17D (Stamaril, Sanofi-Pasteur) (Biological)
Placebo + YF17D at 1 Month
Participants receive placebo (0.9% saline, 0.5 mL IM on Day 0) and yellow fever vaccine YF17D on Day 30.
干预措施: Placebo (NaCl 09%, 0.5mL) (Other)
Placebo + YF17D at 3 Months
Participants receive placebo (0.9% saline, 0.5 mL IM on Day 0) and yellow fever vaccine YF17D on Day 90.
干预措施: YF17D (Stamaril, Sanofi-Pasteur) (Biological)
结局指标
主要结局
Host Immune Response
时间窗: Days 0, 7, 14, 28, 56, 84 (3 months)
Explorative evaluation of host immune response profile (cytokines, immune cell populations, gene expression, epigenetic modifications) induced by AS01 versus placebo, using panel of validated multi-omics assay tests, over a 3-month period.
次要结局
- Viraemia Levels(7 days following yellow fever vaccine administration)
- B Cell Response(30 days)
- T Cell Response(30 days)