Vaccine adjuvants to engage the cross-presentation pathway

Lee, Woo‐Jong; Suresh, M.

doi:10.3389/fimmu.2022.940047

Cited by 57 publications

(38 citation statements)

References 245 publications

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“…TLR signaling from phagosomes has been demonstrated to regulate antigen presentation at the organelle-autonomous level 53 . Therefore, it is possible that upon association of SLP and TLR ligands, intracellular trafficking and/or endosome maturation, and thereby cross-presentation, might still be different for TLR1/2 and TLR3-based adjuvants 54 . Despite these limitations, the identification of a "TRIF" signature in our study does demonstrate DC immunopeptidomics is sufficiently sensitive and reproducible to detect differences between variably treated samples.…”

Section: Discussionmentioning

confidence: 99%

HLA class I peptidome analysis of synthetic long peptide-fed human dendritic cells for therapeutic vaccine design

Buschow,

Kessler,

Doff

et al. 2024

Preprint

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Synthetic long peptides (SLPs) are a promising vaccine modality that exploit dendritic cells (DC) to treat chronic infections or cancer. Currently, the design of SLPs relies on in silico prediction and multifactorial T cells assays to determine which SLPs are best cross-presented on DC human leukocyte antigen class I (HLA-I). Furthermore, it is unknown how TLR ligand-based adjuvants affect DC cross-presentation. Here, we generated a unique, high-quality immunopeptidome dataset of human DCs pulsed with 12 hepatitis B virus (HBV)-based SLPs combined with either a TLR1/2 (Amplivant®) or TLR3 (PolyI:C) ligand. The obtained immunopeptidome reflected adjuvant-induced differences, but no differences in cross-presentation of SLPs. We uncovered dominant (cross-)presentation on B-alleles, and identified 33 unique SLP-derived HLA-I peptides, several of which were not in silico predicted and some were consistently found across donors. Our work puts forward DC immunopeptidomics as a valuable tool for therapeutic vaccine design.

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Section: Discussionmentioning

confidence: 99%

HLA class I peptidome analysis of synthetic long peptide-fed human dendritic cells for therapeutic vaccine design

Buschow,

Kessler,

Doff

et al. 2024

Preprint

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“…In a previous work, we demonstrated that anti- T. cruzi antibodies were able to induce cancer cell death by antibody-dependent cellular cytotoxicity [ 19 ]. Alum, the primary adjuvant licensed for human use since 1920, promotes antibody and Th2 immune responses; likely by storing and allowing the slow release of antigens from the sites of immunisation [ 33 ]. Considering the role of this adjuvant in promoting inflammation and a potent antibody immune response, it would be worth studying whether the parasite lysate in the presence or absence of this adjuvant induces the production of IL-1β and IL-18.…”

Section: Discussionmentioning

confidence: 99%

Trypanosoma cruzi-Derived Molecules Induce Anti-Tumour Protection by Favouring Both Innate and Adaptive Immune Responses

Freire

Landeira

Giacomini

et al. 2022

IJMS

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Lung cancer remains the leading cause of cancer mortality worldwide. Thus, the development of strategies against this type of cancer is of high value. Parasite infections can correlate with lower cancer incidence in humans and their use as vaccines has been recently explored in preclinical models. In this study, we investigated whether immunisations with a Trypanosoma cruzi lysate from epimastigotes protect from lung tumour growth in mice. We also explore the role of parasite glycans in the induction of the protective immune response. A pre-clinical murine cancer model using the lung tumour cell line LL/2 was used to evaluate the anti-tumour potential, both in preventive and therapeutic settings, of a T. cruzi epimastigote-derived protein lysate. Immunisation with the parasite lysate prevents tumour growth and induces both humoral and cellular anti-tumour immune responses to LL-2 cancer cells. The induced immunity and tumour protection were associated with the activation of natural killer (NK) cells, the production of interferon-γ (IFN-γ) and tumour cell cytotoxicity. We also show that mannose residues in the T. cruzi lysate induce Toll-like receptor (TLR) signalling. The evaluated T. cruzi lysate possesses anti-tumour properties likely by activating innate and adaptive immunity in a process where carbohydrates seem to be essential.

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“…pDC is a potent inducer of type I interferon (IFN) and cytokines, inducing systemic inflammation, but it has a low capacity for cross-antigen presentation [ 56 , 77 ]. However, there are opposing views as to pDC antigen presentation capacity in several papers [ 77 , 78 ]. Cross-antigen presentation may occur under the activation of MyD88 in other dendritic cell subsets; TLRs that use MyD88 as an adaptor is not limited to APC expression [ 11 ], and safety issues, along with the side effect of systemic inflammation, are barriers and have not been approved under the Pharmaceutical Affairs Law, except TLR4.…”

Section: Ticam-1 Pathway In Dendritic Cellsmentioning

confidence: 99%

Toward Establishing an Ideal Adjuvant for Non-Inflammatory Immune Enhancement

Seya

Tatematsu

Matsumoto

2022

Cells

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The vertebrate immune system functions to eliminate invading foreign nucleic acids and foreign proteins from infectious diseases and malignant tumors. Because pathogens and cancer cells have unique amino acid sequences and motifs (e.g., microbe-associated molecular patterns, MAMPs) that are recognized as “non-self” to the host, immune enhancement is one strategy to eliminate invading cells. MAMPs contain nucleic acids specific or characteristic of the microbe and are potential candidates for immunostimulants or adjuvants. Adjuvants are included in many vaccines and are a way to boost immunity by deliberately administering them along with antigens. Although adjuvants are an important component of vaccines, it is difficult to evaluate their efficacy ex vivo and in vivo on their own (without antigens). In addition, inflammation induced by currently candidate adjuvants may cause adverse events, which is a hurdle to their approval as drugs. In addition, the lack of guidelines for evaluating the safety and efficacy of adjuvants in drug discovery research also makes regulatory approval difficult. Viral double-stranded (ds) RNA mimics have been reported as potent adjuvants, but the safety barrier remains unresolved. Here we present ARNAX, a noninflammatory nucleic acid adjuvant that selectively targets Toll-like receptor 3 (TLR3) in antigen-presenting dendritic cells (APCs) to safely induce antigen cross-presentation and subsequently induce an acquired immune response independent of inflammation. This review discusses the challenges faced in the clinical development of novel adjuvants.

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Vaccine adjuvants to engage the cross-presentation pathway

Cited by 57 publications

References 245 publications

HLA class I peptidome analysis of synthetic long peptide-fed human dendritic cells for therapeutic vaccine design

HLA class I peptidome analysis of synthetic long peptide-fed human dendritic cells for therapeutic vaccine design

Trypanosoma cruzi-Derived Molecules Induce Anti-Tumour Protection by Favouring Both Innate and Adaptive Immune Responses

Toward Establishing an Ideal Adjuvant for Non-Inflammatory Immune Enhancement

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