Coformulation with Tattoo Ink for Immunological Assessment of Vaccine Immunogenicity in the Draining Lymph Node

Barber-Axthelm, Isaac M; Kelly, Hannah G.; Esterbauer, Robyn; Wragg, Kathleen; Gibbon, Anne; Lee, Wen Shi; Wheatley, Adam K.; Kent, Stephen J.; Tan, Hyon‐Xhi; Juno, Jennifer A

doi:10.4049/jimmunol.2001299

Cited by 6 publications

(3 citation statements)

References 49 publications

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“…Interestingly, we also confirmed an uptake of tattoo ink by lymphocytes as reported before by other groups where the authors demonstrated that although tattoo ink was located in lymph nodes, it did not affect the responses of B and T cells [19]. Moreover, the uptake by granulocytes might be low, but due to their high numbers, it might be important as well.…”

Section: Discussionsupporting

confidence: 91%

Macrophage‐like rapid uptake and toxicity of tattoo ink in human monocytes

Lin,

Marquardt,

Rütten

et al. 2023

Immunology

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Macrophages play a critical role for the persistence of tattoo ink in human skin. However, a comparison to other skin‐resident and blood circulating immune cells and a profound analysis of REACH‐compliant tattoo ink are unmet medical needs. We hence characterized the size distribution of ink particles using physicochemical methods. We studied the uptake of tattoo ink by key human skin cells and blood‐derived immune cells using optical and electron microscopy as well as flow cytometry. Scanning electron microscopy of ink revealed its crystalline structure, and a tendency towards aggregations was indicated by size changes upon diluting it. Flow cytometric analyses of skin and immune cells after incubation with tattoo ink demonstrated an increase in cellular granularity upon uptake and red ink additionally evoked fluorescent signals. Human macrophages were most potent in internalizing ink in full thickness 3D skin models. Macrophage cultures demonstrated that the ink did not lead to elevated inflammatory mediators, and showed no indications for toxicity, even after nice days. Strikingly, monocytes were most efficient in ink uptake, but displayed reduced viability, whereas granulocytes and lymphocytes showed only temporary ink uptake with flow cytometric signals declining after 1 day. Mechanistic studies on ink retention by corticosteroids or dexpanthenol in macrophage cultures demonstrated that these compounds do not lead to ink excretion, but even slightly increase the ink load in macrophages. The highly motile monocytes, precursors of macrophages, may play an underrated role for tattoo ink translocation from dermal blood vessels into internal organs.

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Section: Discussionsupporting

confidence: 91%

Macrophage‐like rapid uptake and toxicity of tattoo ink in human monocytes

Lin,

Marquardt,

Rütten

et al. 2023

Immunology

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“…It should also be noted that we analyzed only inguinal LNs near the site of vaccination. Recent findings suggested that drainage of antigen to inguinal LNs could be variable following IM immunization, while iliac lymph nodes showed better drainage 34 . Generally, the antigen is drained more to LNs that are closest to the site of vaccination, and thus IM immunizations may target deeper LNs compared to ID immunizations.…”

Section: Discussionmentioning

confidence: 99%

Intradermal but not intramuscular modified vaccinia Ankara immunizations protect against intravaginal tier2 simian-human immunodeficiency virus challenges in female macaques

et al. 2023

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Route of immunization can markedly influence the quality of immune response. Here, we show that intradermal (ID) but not intramuscular (IM) modified vaccinia Ankara (MVA) vaccinations provide protection from acquisition of intravaginal tier2 simian-human immunodeficiency virus (SHIV) challenges in female macaques. Both routes of vaccination induce comparable levels of serum IgG with neutralizing and non-neutralizing activities. The protection in MVA-ID group correlates positively with serum neutralizing and antibody-dependent phagocytic activities, and envelope-specific vaginal IgA; while the limited protection in MVA-IM group correlates only with serum neutralizing activity. MVA-ID immunizations induce greater germinal center Tfh and B cell responses, reduced the ratio of Th1 to Tfh cells in blood and showed lower activation of intermediate monocytes and inflammasome compared to MVA-IM immunizations. This lower innate activation correlates negatively with induction of Tfh responses. These data demonstrate that the MVA-ID vaccinations protect against intravaginal SHIV challenges by modulating the innate and T helper responses.

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“…However, it was the prolonged immunogen release that yielded the greatest increase in GC activity and downstream nAb development, though further dose-matched comparisons and an understanding of how well Evans Blue (a small molecule dye) recapitulates formulated vaccine antigen draining is needed. A more recent study has proposed tattoo ink as an alternative for identifying the antigen draining lymph nodes within a lymph node cluster ( 40 ).…”

Section: Non-human Primatesmentioning

confidence: 99%

Human lymphoid tissue sampling for vaccinology

Kwiatkowska

Mkindi²,

Nielsen³

2022

Front. Immunol.

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Long-lived plasma cells (LLPCs) – largely resident in the bone marrow – secrete antibody over months and years, thus maintaining serum antibody concentrations relevant for vaccine-mediated immunity. Little is known regarding factors that can modulate the induction of human LLPC responses in draining lymph node germinal centres, or those that maintain LLPCs in bone marrow niches following vaccination. Here, we review human and non-human primate vaccination studies which incorporate draining lymph node and/or bone marrow aspirate sampling. We emphasise the key contributions these samples can make to improve our understanding of LLPC immunology and guide rational vaccine development. Specifically, we highlight findings related to the impact of vaccine dosing regimens, adjuvant/vaccine platform selection, duration of germinal centre reactions in draining lymph nodes and relevance for timing of tissue sampling, and heterogeneity in bone marrow plasma cell populations. Much of this work has come from recent studies with SARS-CoV-2 vaccine candidates or, with respect to the non-human primate work, HIV vaccine development.

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Coformulation with Tattoo Ink for Immunological Assessment of Vaccine Immunogenicity in the Draining Lymph Node

Cited by 6 publications

References 49 publications

Macrophage‐like rapid uptake and toxicity of tattoo ink in human monocytes

Macrophage‐like rapid uptake and toxicity of tattoo ink in human monocytes

Intradermal but not intramuscular modified vaccinia Ankara immunizations protect against intravaginal tier2 simian-human immunodeficiency virus challenges in female macaques

Human lymphoid tissue sampling for vaccinology

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