AS01B Adjuvant Use and Shingrix-Related DILI Investigation
The AS01B adjuvant is currently used in two FDA-approved vaccines: Shingrix (recombinant zoster vaccine) and Arexvy (respiratory syncytial virus vaccine), so your patient could potentially react to Arexvy as well if re-exposed to AS01B. 1, 2
Understanding AS01B and Its Components
The AS01B adjuvant system in Shingrix contains two key immunostimulants combined in a liposomal formulation 3:
- MPL (3-O-desacyl-4'-monophosphoryl lipid A) - 50 mcg per dose, derived from Salmonella minnesota
- QS-21 - 50 mcg per dose, a saponin purified from Quillaja saponaria Molina plant extract
- Liposomal carriers: dioleoyl phosphatidylcholine (DOPC) and cholesterol
This adjuvant system was specifically designed to enhance both cellular and humoral immune responses, which is why it's highly effective but also more reactogenic than traditional aluminum-based adjuvants 4, 5.
Other Shingrix Components That Could Cause DILI
Beyond AS01B, your patient's liver injury could be attributed to:
1. The Recombinant gE Antigen (50 mcg per dose)
- Produced in Chinese Hamster Ovary (CHO) cells
- Contains residual host cell proteins (≤3.0%) and DNA (≤2.1 picograms) 3
- While less likely than adjuvant components, protein antigens can trigger immune-mediated reactions
2. Excipients and Stabilizers 3:
- Sucrose (20 mg) - stabilizer
- Polysorbate 80 (0.08 mg) - can rarely cause hypersensitivity
- Phosphate buffers (multiple salts)
- Sodium chloride (4.385 mg)
3. Liposomal Components:
- DOPC (1 mg)
- Cholesterol (0.25 mg)
Clinical Approach to Your Patient's DILI
Immediate assessment priorities 6, 7, 8:
Confirm DILI diagnosis by excluding:
- Viral hepatitis (A, B, C, E; also CMV, EBV, HSV if immunocompromised)
- Autoimmune hepatitis markers (ANA, ASMA, quantitative immunoglobulins)
- Other medications, herbal supplements, alcohol
- Hepatobiliary imaging to rule out structural causes
Document the pattern and severity:
- Hepatocellular vs. cholestatic vs. mixed pattern
- Whether Hy's Law criteria met (ALT ≥3× ULN with symptoms OR ≥5× ULN without symptoms)
- Presence of hypersensitivity features (rash, fever, eosinophilia)
Temporal relationship: DILI from vaccines typically occurs within days to weeks post-vaccination, though immune-mediated reactions can have variable latency 6
Critical Management Decisions
Your patient should NOT receive:
- The second dose of Shingrix 9, 10
- Arexvy (RSV vaccine containing AS01E, a similar adjuvant system) 2
- Consider caution with other adjuvanted vaccines
Regarding other vaccines 1, 2:
- Non-adjuvanted vaccines (standard influenza, pneumococcal, COVID-19 mRNA vaccines) should be safe
- The AS01B-specific reaction doesn't contraindicate aluminum-adjuvanted vaccines
- MF59-adjuvanted influenza vaccine (Fluad) uses a different adjuvant system and may be considered, though data on cross-reactivity are limited
Important Caveats
The AS01B adjuvant is known to be highly reactogenic 11, 12:
- Grade 3 injection site reactions occur in ~9.5% of recipients
- Grade 3 systemic symptoms in ~11.4%
- Most reactions are transient (resolve within 4 days)
- However, true DILI is extremely rare and not well-characterized in the literature
The challenge here is distinguishing between:
- True drug-induced liver injury requiring permanent avoidance
- Coincidental liver injury from another cause
- Immune-mediated hepatitis triggered by the vaccine's immunostimulatory effects 13, 14
If your patient had features suggesting immune-mediated hepatitis (elevated autoantibodies, interface hepatitis on biopsy if performed), this represents a more concerning pattern that absolutely contraindicates rechallenge 6, 8.
Document this adverse event in VAERS (Vaccine Adverse Event Reporting System) to contribute to pharmacovigilance data, as vaccine-associated DILI remains poorly characterized and underreported 9, 10.