AS01 adjuvant to boost immune protection in adults

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

This study tries a single dose of the AS01 adjuvant in healthy adults aged 21–59 to see if it strengthens and trains the immune system and improves response to a later viral vaccine.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 40 (estimated)
• Ages: 21 Years to 59 Years
• Sex: All
• Sponsor: Singapore General Hospital (Academic / other)
• Locations: 1 site (Singapore)
• Trial ID: NCT07527247 on ClinicalTrials.gov

What this trial studies

This single-center, randomized, single-blind, placebo-controlled Phase 2 study at Singapore General Hospital will enroll 40 healthy adults aged 21–59. Participants receive one intramuscular dose of AS01 (0.5 mL) or saline placebo on Day 0, then a licensed live-attenuated yellow fever vaccine (YF17D) at either 1 month or 3 months to model a controlled viral exposure. Serial blood sampling over approximately 2–4 months will measure innate and adaptive immune reprogramming, the durability of any effect, and the immune response to the viral challenge. The design tests whether AS01 alone can induce trained immunity that translates into better control of a heterologous viral infection.

Who should consider this trial

Good fit: Ideal candidates are healthy adults aged 21–59 with BMI 18.5–27.5, stable medical conditions if present, an accessible forearm vein for blood draws, and the ability to attend scheduled visits and comply with study procedures.

Not a fit: People older than 59, those with unstable medical conditions, immunocompromised individuals, pregnant or breastfeeding people, or those outside the specified BMI range are unlikely to be eligible or to gain benefit from this study.

Why it matters

Potential benefit: If successful, AS01 could be used as a standalone immune booster to rapidly increase broad protection against unrelated infections, helping with outbreak preparedness and reducing the risk of severe disease.

How similar studies have performed: AS01 is an approved adjuvant used in licensed vaccines like the shingles vaccine and has clear immune-activating effects, but using AS01 alone to induce trained immunity and broad protection is largely untested in humans.

Eligibility criteria

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.

Where this trial is running

Singapore

• Singapore General Hospital — Singapore, Singapore (Recruiting)

Study contacts

• Principal investigator: Candice Y.Y. Chan, MBChB, MRCP — Singapore General Hospital
• Study coordinator: Candice Y.Y. Chan, MBChB, MRCP

Conditions Immune System Responses and Trained Immunity After AS01 Administration; Healthy Adult; AS01; AS01 adjuvant; Immune durability; Immune system; Immune response modulation; Recombinant zoster vaccine adjuvant