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 and generates trained immunity in monocytes and NK cells, but direct measurement of innate responses is severely limited with only one of ten studies directly assessing these mechanisms.
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 and epigenetic modifications including decreased TGFβ pathway accessibility. Mechanistically, AS01B stimulates local innate activation through TLR4 signaling (MPL) and cytokine induction (QS-21), synergistically recruiting and activating 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. Records from Elicit search
- n = 200
- Papers screened using: Vaccine Type, Innate Immune Parameters, Study Population, Comparison Groups, Quantitative Measures, Study Design, Publication Type
- n = 200 Papers screened out
- n = 190 Papers included for extraction
Paper search
We performed a semantic search across over 138 million academic papers from the Elicit search engine, which includes all of Semantic Scholar and OpenAlex.
We ran this query: "Zoster Vaccine Recombinant, Adjuvanted AS01B adjuvant innate immune activation"
The search returned 200 total results from Elicit.
Screening
We screened in sources based on their abstracts that met several criteria, including vaccine type, innate immune parameters, study population, comparison groups, quantitative measures, study design, and publication type.
Data extraction
We asked a large language model to extract each data column below from each paper. We gave the model the extraction instructions for various columns concerning study population, vaccine formulation, innate immunity measurements, adaptive immunity, safety profile, study methodology, adjuvant mechanisms, moderating factors, and clinical outcomes.
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 | Comparison 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 (mean 72.3) | 70 participants | 9-year immune persistence |
| Hastie et al., 2020 | Yes | Phase IIIB open-label extension | Adults vaccinated at ≥60 years (mean 82.6 at additional dosing) | 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 |
All studies evaluated the recombinant zoster vaccine containing varicella-zoster virus glycoprotein E antigen with AS01B adjuvant system. The vaccine was administered as a two-dose schedule, with doses given 1-2 months apart.
Direct Innate Immune Activation Measurements
Only one study directly measured innate immune responses to RZV. Johnson et al. (2024) assessed innate immune cell activation in 10-14 vaccinees, measuring B cell, monocyte, and dendritic cell (DC) responses. These innate responses demonstrated two-phase kinetics: a transient increase post-dose 1 and a persistent increase post-dose 2 lasting up to 1 year.
Mechanistic Basis of AS01B Adjuvant Activity
While most studies did not directly measure innate immune activation, Cunningham et al. (2018) described the mechanistic basis of AS01B function. The AS01B adjuvant system stimulates local and transient activation of the innate response.
Adaptive Immune Responses as Markers of Adjuvant Function
Humoral Immune Responses
Across studies in immunocompetent adults, RZV induced robust anti-gE antibody responses.
Cell-Mediated Immune Responses
RZV induced strong CD4+ T-cell responses across studies.
Anamnestic Responses
Hastie et al. (2020) evaluated the immunogenicity of additional RZV doses administered 10 years after initial vaccination in participants.
Safety Profile and Reactogenicity
Reactogenicity provides indirect evidence of innate immune activation. Pain was the most frequent local solicited adverse event, reported by 48.2% of participants.
Clinical Efficacy
RZV demonstrated high vaccine efficacy against herpes zoster across diverse populations, with high efficacy in NHBCL patients despite lower humoral responses, suggesting that cell-mediated immune responses are the main mechanistic driver for protection.
Factors Influencing Adjuvant Response
Age Effects
Most studies found minimal age effects on RZV-induced immune responses.
Immunosuppression Effects
Immunosuppression affected adjuvant responses differentially depending on the mechanism.
Synthesis
This systematic review identified a gap between the robust clinical efficacy and adaptive immune responses induced by RZV and the limited direct measurement of innate immune activation. The observation that NHBCL patients showed high efficacy despite low antibody responses suggests that CMI responses—and by extension, the innate priming that generates them—are the critical correlates of protection.