Establishment of a novel safety assessment method for vaccine adjuvant development

Momose, Haruka; Hiradate, Yuki; Mizukami, Tamio; Hamaguchi, Isao

doi:10.1016/j.vaccine.2018.10.009

Cited by 13 publications

(10 citation statements)

References 86 publications

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“…47−50 Although these adjuvant candidates exhibit robust potency, they are also limited by high risks of toxicity. 51 Besides, the loading of exogenous adjuvants is often performed by aggressive methods, such as electroporation and sonication, which make it difficult to ensure the integrity of cell-derived components, thereby weakening or losing the function of cell-derived components and reducing the efficacy of the nanovaccine. 13,14 The adjuvant Hsp70s contained in αM-Exos are endogenous components from cells, thus eliminating the risk of toxicity arising from exogenous adjuvant.…”

Section: Discussionmentioning

confidence: 99%

“…Generally, adjuvants are essential for cancer nanovaccines, which are administrated together with tumor antigens to potentiate antigen-specific immune responses. Most of the existing tumor cell-derived cancer nanovaccines are loaded with exogenous adjuvants, such as CpG ODN, Poly(I:C), and R848. − Although these adjuvant candidates exhibit robust potency, they are also limited by high risks of toxicity . Besides, the loading of exogenous adjuvants is often performed by aggressive methods, such as electroporation and sonication, which make it difficult to ensure the integrity of cell-derived components, thereby weakening or losing the function of cell-derived components and reducing the efficacy of the nanovaccine. , The adjuvant Hsp70s contained in αM-Exos are endogenous components from cells, thus eliminating the risk of toxicity arising from exogenous adjuvant.…”

Section: Discussionmentioning

confidence: 99%

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Biologically Self-Assembled Tumor Cell-Derived Cancer Nanovaccines as an All-in-One Platform for Cancer Immunotherapy

Liang,

Sun,

Xie

et al. 2024

ACS Nano

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Tumor cell-derived cancer nanovaccines introduce tumor cell-derived components as functional units that endow the nanovaccine systems with some advantages, especially providing all potential tumor antigens. However, cumbersome assembly steps, potential risks of exogenous adjuvants, as well as insufficient lymph node (LN) targeting and dendritic cell (DC) internalization limit the efficacy and clinical translation of existing tumor cell-derived cancer nanovaccines. Herein, we introduced an endoplasmic reticulum (ER) stress inducer αmangostin (αM) into tumor cells through poly(D, L-lactide-coglycolide) nanoparticles and harvested biologically self-assembled tumor cell-derived cancer nanovaccines (αM-Exos) based on the biological process of tumor cell exocytosing nanoparticles through tumor-derived exosomes (TEXs). Besides presenting multiple potential antigens, αM-Exos inherited abundant 70 kDa heat shock proteins (Hsp70s) upregulated by ER stress, which can not only act as endogenous adjuvants but also improve LN targeting and DC internalization. Following subcutaneous injection, αM-Exos efficiently migrated to LNs and was expeditiously endocytosed by DCs, delivering tumor antigens and adjuvants to DCs synchronously, which then powerfully triggered antitumor immune responses and established long-term immune memory. Our study exhibited an all-in-one biologically self-assembled tumor cell-derived cancer nanovaccine platform, and the fully featured cancer nanovaccines assembled efficiently through this platform are promising for desirable cancer immunotherapy.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Biologically Self-Assembled Tumor Cell-Derived Cancer Nanovaccines as an All-in-One Platform for Cancer Immunotherapy

Liang,

Sun,

Xie

et al. 2024

ACS Nano

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“…These are advantageous reasons to choose sublingual roots for mucosal immune response. Furthermore, the above-mentioned side effects of poly(I:C) adjuvant were reported in nasal vaccination using rodent model [ 11 , 12 , 14 ]. These side effects would be affected with differences of adjuvant reactivity between rodents and primates due to the dissimilarity in their immune and related systems [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

SARS-CoV-2 sublingual vaccine with RBD antigen and poly(I:C) adjuvant: Preclinical study in cynomolgus macaques

Yamamoto,

Tanji,

Mitsunaga

et al. 2023

Biology Methods and Protocols

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Mucosal vaccine for sublingual route was prepared with recombinant SARS-CoV-2 spike protein receptor binding domain (RBD) antigen and poly(I:C) adjuvant components. The efficacy of this sublingual vaccine was examined using Cynomolgus macaques. Nine of the macaque monkeys were divided into three groups of three animals: control [just 400 µg poly(I:C) per head], low dose [30 µg RBD and 400 µg poly(I:C) per head], and high dose [150 µg RBD and 400 µg poly(I:C) per head], respectively. N-acetylcysteine (NAC), a mild reducing agent losing mucin barrier, was used to enhance vaccine delivery to mucosal immune cells. RBD-specific IgA antibody secreted in pituita was detected in two of three monkeys of the high dose group and one of three animals of the low dose group. RBD-specific IgG and/or IgA antibodies in plasma were also detected in these monkeys. These indicated that the sublingual vaccine stimulated mucosal immune response to produce antigen-specific secretory IgA antibodies in pituita and/or saliva. This sublingual vaccine also affected systemic immune response to produce IgG (IgA) in plasma. Little RBD-specific IgE was detected in plasma, suggesting no allergic antigenicity of this sublingual vaccine. Thus, SARS-CoV-2 sublingual vaccine consisting of poly(I:C) adjuvant showed reasonable efficacy in a non-human primate model.

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“…Vaccinations through these routes often show higher efficacy than conventional subcutaneous vaccinations. Although nasal vaccines have been established and partly employed for clinical use [9], unpreferable influences to brain/central nerve system or lung were reported by its nasal administration [10][11][12]. On the one hand oral/sublingual vaccine revealed reasonable efficacy and high safety without the influences to brain [13].…”

Section: Introductionmentioning

confidence: 99%

SARS-CoV-2 Sublingual Vaccine with RBD Antigen and Poly(I:C) Adjuvant: Preclinical Study in Cynomolgus Macaques

Yamamoto

Tanji

Mitsunaga³

et al. 2022

Preprint

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Mucosal vaccine for sublingual route was prepared with recombinant SARS-CoV-2 spike protein receptor binding domain (RBD) antigen and poly(I:C) adjuvant components. The efficacy of this sublingual vaccine was examined using Cynomolgus macaques. Nine of the macaque monkeys were divided into three groups of three animals; control (just 400 μg poly(I:C) per head); low dose (30 μg RBD and 400 μg poly(I:C) per head); and high dose (150 μg RBD and 400 μg poly(I:C) per head), respectively. N-acetylcysteine (NAC), a mild reducing agent losing mucin barrier, was used to enhance vaccine delivery to mucosal immune cells. RBD-specific IgA antibody secreted in pituita was detected in two of three monkeys of the high dose group and one of three animals of the low dose group. RBD-specific IgG and/or IgA antibodies in plasma were also detected in these monkeys. These indicated that the sublingual vaccine stimulated mucosal immune response to produce antigen-specific secretory IgA antibodies in pituita and/or saliva. This sublingual vaccine also affected systemic immune response to produce IgG (IgA) in plasma. Little RBD-specific IgE was detected in plasma, suggesting no allergic antigenicity of this sublingual vaccine. Thus, SARS-CoV-2 sublingual vaccine consisting of poly(I:C) adjuvant showed reasonable efficacy in a non-human primate model.

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Establishment of a novel safety assessment method for vaccine adjuvant development

Cited by 13 publications

References 86 publications

Biologically Self-Assembled Tumor Cell-Derived Cancer Nanovaccines as an All-in-One Platform for Cancer Immunotherapy

Biologically Self-Assembled Tumor Cell-Derived Cancer Nanovaccines as an All-in-One Platform for Cancer Immunotherapy

SARS-CoV-2 sublingual vaccine with RBD antigen and poly(I:C) adjuvant: Preclinical study in cynomolgus macaques

SARS-CoV-2 Sublingual Vaccine with RBD Antigen and Poly(I:C) Adjuvant: Preclinical Study in Cynomolgus Macaques

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