ArticleThe Journal of clinical investigation2024
Innate immune cell activation by adjuvant AS01 in human lymph node explants is age independent.
Article in The Journal of clinical investigation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
12 citing papers in PubMed.
- Age-related differences in immune responses to inactivated influenza and adjuvanted recombinant herpes zoster vaccines.JCI insight · 2026Trial
- Rescuing age-associated vaccine hyporesponsiveness in murine and nonhuman primate models with an immunostimulatory vaccine adjuvant.Human vaccines & immunotherapeutics · 2026Article
- Macrophage heterogeneity in human secondary lymphoid organs.Clinical science (London, England : 1979) · 2026Review
- Review
- Review
- Age-related differences in mRNA vaccine immunogenicity and adjuvancy.Immunology and cell biology · 2026Article
- Viral infection states, immune control, and adult cognition: evidence across latency, persistence, and post-acute responses.Frontiers in immunology · 2026Review
- Dissecting the mechanism of action of the adjuvant system AS01 in human immune cells: synergy of QS-21 and monophosphoryl lipid A and role of type I interferons.Frontiers in immunology · 2026Article
- Current status of immunisation for herpes zoster.Human vaccines & immunotherapeutics · 2025Review
- High seroprevalence and high risk: why are older adults more prone to respiratory syncytial virus?Journal of virology · 2025Review
- Ex vivo model of functioning human lymph node reveals role for innate lymphocytes and stroma in response to vaccine adjuvant.Cell reports · 2025Article
- From bark to bench: innovations in QS-21 adjuvant characterization and manufacturing.Frontiers in immunology · 2025Review
Corrections and comments
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Authors and funding
15 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Vaccine adjuvants are thought to work by stimulating innate immunity in the draining lymph node (LN), although this has not been proven in humans. To bridge the data obtained in animals to humans, we have developed an in situ human LN explant model to investigate how adjuvants initiate immunity. Slices of explanted LNs were exposed to vaccine adjuvants and revealed responses that were not detectable in LN cell suspensions. We used this model to compare the liposome-based AS01 with its components, monophosphoryl lipid A (MPL) and QS-21, and TLR ligands. Liposomes were predominantly taken up by subcapsular sinus-lining macrophages, monocytes, and DCs. AS01 induced DC maturation and a strong proinflammatory cytokine response in intact LN slices but not in dissociated cell cultures, in contrast to R848. This suggests that the onset of the immune response to AS01 required a coordinated activation of LN cells in time and space. Consistent with the robust immune response observed in older adults with AS01-adjuvanted vaccines, the AS01 response in human LNs was independent of age, unlike the response to R848. This human LN explant model is a valuable tool for studying the mechanism of action of adjuvants in humans and for screening new formulations to streamline vaccine development.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.