Improving Vaccine Protection for Adults

May 14, 2026 updated by: Singapore General Hospital

Using AS01 Adjuvant to Improve Immune Response in Older Adults Through Trained Immunity

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Estimated)

40

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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 criteria62.
  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: AS01 + YF17D at 1 Month
Participants receive AS01 (0.5 mL IM on Day 0) and yellow fever vaccine YF17D on Day 30.
Biological: AS01 adjuvant (0.5 mL intramuscular)
The AS01 suspension contains 50mg of 3-O-desacyl-4'monophosphoryl lipid A (MPL) and 50mg of Quillaja Saponaria Molina, fraction 21 (QS21), licensed by GSK, available as a separate vial from the licensed Shingrix vaccine.
Biological: YF17D (Stamaril, Sanofi-Pasteur)
Stamaril, the live-attenuated yellow fever vaccine, utilises the YF17D strain. Stamaril is supplied in the form of powder and solvent for suspension for injection in pre-filled syringe, Yellow fever vaccine (live).
Other Names:
  • YF17D
  • yellow fever vaccine
Experimental: AS01 + YF17D at 3 Months
Participants receive AS01 (0.5 mL IM on Day 0) and yellow fever vaccine YF17D on Day 90.
Biological: AS01 adjuvant (0.5 mL intramuscular)
The AS01 suspension contains 50mg of 3-O-desacyl-4'monophosphoryl lipid A (MPL) and 50mg of Quillaja Saponaria Molina, fraction 21 (QS21), licensed by GSK, available as a separate vial from the licensed Shingrix vaccine.
Biological: YF17D (Stamaril, Sanofi-Pasteur)
Stamaril, the live-attenuated yellow fever vaccine, utilises the YF17D strain. Stamaril is supplied in the form of powder and solvent for suspension for injection in pre-filled syringe, Yellow fever vaccine (live).
Other Names:
  • YF17D
  • yellow fever vaccine
Placebo Comparator: 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.
Biological: YF17D (Stamaril, Sanofi-Pasteur)
Stamaril, the live-attenuated yellow fever vaccine, utilises the YF17D strain. Stamaril is supplied in the form of powder and solvent for suspension for injection in pre-filled syringe, Yellow fever vaccine (live).
Other Names:
  • YF17D
  • yellow fever vaccine
Other: Placebo (NaCl 09%, 0.5mL)
The placebo will consist of 0.9% saline solution in equivalent volume.
Other Names:
  • Placebo
  • Saline injection
  • Saline placebo
Placebo Comparator: 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.
Biological: YF17D (Stamaril, Sanofi-Pasteur)
Stamaril, the live-attenuated yellow fever vaccine, utilises the YF17D strain. Stamaril is supplied in the form of powder and solvent for suspension for injection in pre-filled syringe, Yellow fever vaccine (live).
Other Names:
  • YF17D
  • yellow fever vaccine
Other: Placebo (NaCl 09%, 0.5mL)
The placebo will consist of 0.9% saline solution in equivalent volume.
Other Names:
  • Placebo
  • Saline injection
  • Saline placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Host Immune Response
Time Frame: 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.
Days 0, 7, 14, 28, 56, 84 (3 months)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Viraemia Levels
Time Frame: 7 days following yellow fever vaccine administration
Measure Yellow Fever viraemia levels via quantitative RT-PCR and calculate area under the curve (AUC) up to 7 days following yellow fever vaccine administration in AS01 versus placebo recipients.
7 days following yellow fever vaccine administration
B Cell Response
Time Frame: 30 days
Assess B cell responses to yellow fever by measurement of neutralising antibodies titres using plaque reduction neutralization test (PRNT) with sera at day 30 compared with pre-vaccination day 0, following yellow fever vaccine administration in AS01 versus placebo recipients.
30 days
T Cell Response
Time Frame: 30 days
Assess T cell responses to yellow fever vaccine using virus-specific IFNγ ELISPOT assay, with results expressed as spot-forming units (SFU) per 10^6 PBMCs at day 14 and day 30 versus pre-vaccination at day 9 in AS01 versus placebo recipients.
30 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Singapore General Hospital

Collaborators

A*STAR Infectious Diseases Labs

Investigators

  • Principal Investigator: Candice Y.Y. Chan, MBChB, MRCP, Singapore General Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 6, 2025

Primary Completion (Estimated)

February 28, 2029

Study Completion (Estimated)

February 28, 2029

Study Registration Dates

First Submitted

March 4, 2026

First Submitted That Met QC Criteria

April 6, 2026

First Posted (Actual)

April 14, 2026

Study Record Updates

Last Update Posted (Actual)

May 18, 2026

Last Update Submitted That Met QC Criteria

May 14, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AS01-YF-01
  • CIRG25jan-0068 (Other Grant/Funding Number: NMRC)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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