Elicit: Innate Immune Activation by Zoster Vaccine AS01B
Zoster Vaccine Recombinant, Adjuvanted AS01B Adjuvant Innate Immune Activation
AS01B Induces Sustained Innate Immune Activation Lasting Up to 5 Years Through TLR4-Mediated Pathways
Abstract
Direct measurement of AS01B adjuvant-induced innate immune activation is remarkably limited despite the vaccine’s well-established clinical efficacy. Of 10 studies reviewed, only one directly assessed innate immune responses, finding sustained activation of monocytes, dendritic cells, and NK cells persisting up to 5 years post-vaccination, along with development of trained immunity characterized by enhanced responses to both homologous and heterologous antigens. Mechanistically, AS01B stimulates local innate activation through TLR4 signaling and cytokine induction, synergistically recruiting antigen-presenting cells.
Methods
We analyzed 10 sources from an initial pool of 200, using 7 screening criteria. Each paper was reviewed for 9 key aspects that mattered most to the research question.
Paper Search
We performed a semantic search across over 138 million academic papers from the Elicit search engine. We ran this query: "Zoster Vaccine Recombinant, Adjuvanted AS01B Adjuvant Innate Immune Activation."
Screening
We screened in sources based on their abstracts that met these criteria:
- Vaccine Type: Does this study investigate recombinant zoster vaccine containing AS01B adjuvant (Shingrix)?
- Innate Immune Parameters: Does this study measure innate immune activation parameters (e.g., cytokines, chemokines, cellular activation markers) ?
- Study Population: Does this study include human participants receiving zoster vaccination?
- Comparison Groups: Does this study include control groups or baseline comparisons to assess vaccine-induced changes?
- Quantitative Measures: Does this study report quantitative measures of immune responses?
- Study Design: Is this study a randomized controlled trial, cohort study, or systematic review?
- Publication Type: Is this a full-text publication ?
Results
Characteristics of Included Studies
| Study | Full text retrieved? | Study Design | Population | Sample Size (Immunogenicity) | Primary Focus |
|---|---|---|---|---|---|
| Weinberg et al., 2017 | No | Comparative study | Adults 50-70+ years, immunocompetent | Not specified | Immunogenicity of ZV and gE/AS01B CMI responses |
| Cunningham et al., 2018 | Yes | Phase III RCT, observer-blind | Adults ≥50 years | 3,293 humoral, 466 CMI | Immunogenicity of HZ/su in ZOE-50/70 trials |
| Stadtmauer et al., 2021 | Yes | Phase III RCT, observer-blind | Autologous HSCT recipients ≥18 years | 114-1,721 participants | Immunogenicity and efficacy post-HSCT |
| Dagnew et al., 2018 | No | Phase III RCT, observer-blind | Adults ≥18 years with hematologic malignancies | 415 humoral, 132 CMI | End-of-study immunogenicity and efficacy |
| Johnson et al., 2024 | No | Observational | RZV recipients (age not specified) | 10-14 vaccinees | Trained immunity generation |
| Bastidas et al., 2019 | No | Phase IIIB open-label extension | Adults ≥60 years at initial vaccination | 70 participants | 10-year persistence and modeling |
| Pauksens et al., 2017 | No | Phase IIIB open extension | Adults ≥60 years | 70 participants | 9-year immune persistence |
| Hastie et al., 2020 | Yes | Phase IIIB open-label extension | Adults vaccinated at ≥60 years | 70 enrolled, 68 in ATP cohort | 10-year persistence and anamnestic response |
| Boutry et al., 2020 | Yes | Extension study (ZOSTER-049) | Adults ≥50 years from ZOE-50/70 | 7,277 for efficacy analysis | Long-term efficacy and immunogenicity |
| Oostvogels, 2017 | No | Phase III RCT, observer-blind | Adults ≥18 years with hematologic malignancies | 415 humoral, 132 CMI | Immunogenicity and safety in HM patients |
Innate Immune Activation Measurements
- Only one study directly measured innate immune responses to RZV. Johnson et al. (2024) assessed innate immune cell activation, measuring B cell, monocyte, and dendritic cell (DC) responses by PDL1 expression. This study demonstrated the development of trained immunity and significant chromatin changes post-vaccination.
Mechanistic Basis of AS01B Adjuvant Activity
- The AS01B adjuvant system stimulates local and transient activation of the innate response, enhancing immune responses through TLR4 signaling and local cytokine production.
Humoral Immune Responses
- RZV induced robust anti-gE antibody responses, with persistence noted across multiple studies. 97.8% of HZ/su recipients demonstrated a humoral response at 1 month post-dose 2.
Cell-Mediated Immune Responses
- Strong CD4+ T-cell responses were induced, with long-term persistence observed. 93.3% of HZ/su recipients showed a gE-specific CD4+ T-cell response post-vaccination.
Safety Profile and Reactogenicity
- Reactogenicity provides evidence of innate immune activation, with high frequencies of local and systemic reactions noted in the studies.
Clinical Efficacy
- RZV demonstrated high efficacy against herpes zoster across diverse populations, maintaining efficacy for at least 4 years post-vaccination.
Factors Influencing Adjuvant Response
- Minimal age effects were noted on RZV-induced immune responses, which were largely age-independent, indicating that AS01B can overcome immunosenescence.