CAF01 liposomes as a mucosal vaccine adjuvant: In vitro and in vivo investigations

Toll-like receptor (TLR) ligands are being developed for use as vaccine adjuvants and as immunomodulators because of their ability to stimulate innate and adaptive immune responses. Flagellin, a TLR5 ligand, was reported to show potent mucosal vaccine adjuvant activity. To identify ligands that potentiate the adjuvant activity of flagellin, we screened a plant library using HEK293T cells transiently cotransfected with phTLR5 and pNF-κB-SEAP plasmids. The 90% EtOH extract fromCroton tigliumshowed significant NF-κB transactivation in a TLR5-independent manner along with the increase of a flagellin activity. We have studied to characterize an active component fromCroton tigliumand to elucidate the action mechanisms. Phorbol 12-myristate 13-acetate (PMA) was isolated as an active component ofCroton tigliumby activity-guided fractionation, column chromatography, HPLC, NMR, and MS. PMA at a range of nM induced PKC-dependent NF-κB activation and IL-8 production in both TLR5− and TLR5+ assay systems. In in vivo mouse vaccination model, PMA induced antigen-specific IgG and IgA antibody responses and increased IL-12 production corresponding to T cell responses in spleen lymphocytes. These results suggest that PMA would serve as an efficacious mucosal vaccine adjuvant.

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Nanoparticles assembled from fucoidan and trimethylchitosan as anthrax vaccine adjuvant: In vitro and in vivo efficacy in comparison to CpG

Carbohydrate Polymers ◽

10.1016/j.carbpol.2020.116041 ◽

2020 ◽

Vol 236 ◽

pp. 116041 ◽

Cited By ~ 3

Author(s):

Meng-hung Tsai ◽

Chuan-chang Chuang ◽

Cheng-cheung Chen ◽

Hui-ju Yen ◽

Kuang-ming Cheng ◽

...

Keyword(s):

Vaccine Adjuvant ◽

In Vivo Efficacy ◽

Anthrax Vaccine

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Trivalent Vaccine against Botulinum Toxin Serotypes A, B, and E That Can Be Administered by the Mucosal Route

Infection and Immunity ◽

10.1128/iai.01893-06 ◽

2007 ◽

Vol 75 (6) ◽

pp. 3043-3054 ◽

Cited By ~ 71

Author(s):

Easwaran Ravichandran ◽

Fetweh H. Al-Saleem ◽

Denise M. Ancharski ◽

Mohammad D. Elias ◽

Ajay K. Singh ◽

...

Keyword(s):

Botulinum Toxin ◽

Immunoglobulin A ◽

Mucosal Vaccine ◽

Human Illness ◽

Epithelial Barriers ◽

High Level ◽

Carboxy Terminal ◽

Trivalent Vaccine

ABSTRACT Most reports dealing with vaccines against botulinum toxin have focused on the injection route of administration. This is unfortunate, because a mucosal vaccine is likely to be more efficacious for patients and pose fewer risks to health care workers and to the environment. Therefore, efforts were made to generate a mucosal vaccine that provides protection against the botulinum serotypes that typically cause human illness (serotypes A, B, and E). This work demonstrated that carboxy-terminal peptides derived from each of the three serotypes were able to bind to and penetrate human epithelial barriers in vitro, and there was no cross inhibition of membrane binding and transcytosis. The three polypeptides were then tested in vivo as a trivalent vaccine that could be administered to mice by the intranasal route. The results indicated that the mucosal vaccine evoked high secretory titers of immunoglobulin A (IgA), as well as high circulating titers of IgG and IgA, and it also evoked a high level of resistance to challenge with toxin. The immunoglobulin responses and the levels of resistance to challenge were increased by coadministration of adjuvants, such as chitosan and vitamin E. At least three mechanisms were identified to account for the antibody-induced resistance: (i) blockade of toxin absorption across epithelial cells, (ii) enhanced clearance of toxin from the circulation, and (iii) blockade of toxin action at the neuromuscular junction. These results are a compelling demonstration that a mucosal vaccine against multiple serotypes of botulinum toxin has been identified.

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Cholera Toxin Induces a Shift from Inactive to Active Cyclooxygenase 2 in Alveolar Macrophages Activated by Mycobacterium bovis BCG

Infection and Immunity ◽

10.1128/iai.01031-12 ◽

2012 ◽

Vol 81 (1) ◽

pp. 373-380

Author(s):

Mari Kogiso ◽

Tsutomu Shinohara ◽

C. Kathleen Dorey ◽

Yoshimi Shibata

Keyword(s):

Cholera Toxin ◽

Mycobacterium Bovis ◽

Alveolar Macrophages ◽

Mucosal Vaccine ◽

Prostaglandin E ◽

Lung Cells ◽

Cox 2 ◽

Cox 1

Intranasal vaccination stimulates formation of cyclooxygenases (COX) and release of prostaglandin E2(PGE2) by lung cells, including alveolar macrophages. PGE2plays complex pro- or anti-inflammatory roles in facilitating mucosal immune responses, but the relative contributions of COX-1 and COX-2 remain unclear. Previously, we found thatMycobacterium bovisBCG, a human tuberculosis vaccine, stimulated increased release of PGE2by macrophages activatedin vitro; in contrast, intranasal BCG activated no PGE2release in the lungs, because COX-1 and COX-2 in alveolar macrophages were subcellularly dissociated from the nuclear envelope (NE) and catalytically inactive. This study tested the hypothesis that intranasal administration of BCG with cholera toxin (CT), a mucosal vaccine component, would shift the inactive, NE-dissociated COX-1/COX-2 to active, NE-associated forms. The results showed increased PGE2release in the lungs and NE-associated COX-2 in the majority of COX-2+macrophages. These COX-2+macrophages were the primary source of PGE2release in the lungs, since there was only slight enhancement of NE-associated COX-1 and there was no change in COX-1/COX-2 levels in alveolar epithelial cells following treatment with CT and/or BCG. To further understand the effect of CT, we investigated the timing of BCG versus CT administration forin vivoandin vitromacrophage activations. When CT followed BCG treatment, macrophagesin vitrohad elevated COX-2-mediated PGE2release, but macrophagesin vivoexhibited less activation of NE-associated COX-2. Our results indicate that inclusion of CT in the intranasal BCG vaccination enhances COX-2-mediated PGE2release by alveolar macrophages and further suggest that the effect of CTin vivois mediated by other lung cells.

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Induction of Potent Adaptive Immunity by the Novel Polyion Complex Nanoparticles

Clinical and Vaccine Immunology ◽

10.1128/cvi.00080-15 ◽

2015 ◽

Vol 22 (5) ◽

pp. 578-585 ◽

Cited By ~ 5

Author(s):

Tomofumi Uto ◽

Takami Akagi ◽

Mitsuru Akashi ◽

Masanori Baba

Keyword(s):

Cationic Polymer ◽

Water Soluble ◽

Vaccine Adjuvant ◽

Antigen Delivery ◽

Cationic Polymers ◽

Immunostimulatory Activity ◽

Polyion Complex ◽

Biodegradable Poly

ABSTRACTThe development of effective and simple methods of vaccine preparation is desired for the prophylaxis and treatment of a variety of infectious diseases and cancers. We have created novel polyion complex (PIC) nanoparticles (NPs) composed of amphiphilic anionic biodegradable poly(γ-glutamic acid) (γ-PGA) and cationic polymers as a vaccine adjuvant. PIC NPs can be prepared by mixing γ-PGA-graft-l-phenylalanine ethylester (γ-PGA-Phe) polymer with cationic polymer in phosphate-buffered saline. We examined the efficacy of PIC NPs for antigen delivery and immunostimulatory activityin vitroandin vivo. PIC NPs enhanced the uptake of ovalbumin (OVA) by dendritic cells (DCs) and subsequently induced DC maturation. The immunization of mice with OVA-carrying PIC NPs induced potent and antigen-specific cellular and humoral immunity. Since PIC NPs can be created with water-soluble anionic γ-PGA-Phe and a cationic polymer by simple mixing in the absence of any organic solvents, PIC NPs may have potential as a novel candidate for an effective antigen carrier and vaccine adjuvant.

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The mucosal adjuvant cyclic di-GMP enhances antigen uptake and selectively activates pinocytosis-efficient cells in vivo

eLife ◽

10.7554/elife.06670 ◽

2015 ◽

Vol 4 ◽

Cited By ~ 32

Author(s):

Steven M Blaauboer ◽

Samira Mansouri ◽

Heidi R Tucker ◽

Hatti L Wang ◽

Vincent D Gabrielle ◽

...

Keyword(s):

Streptococcus Pneumoniae ◽

Cyclic Gmp ◽

Mucosal Vaccine ◽

Vaccine Adjuvant ◽

Vaccine Response ◽

Antigen Uptake ◽

Mucosal Adjuvant ◽

Adjuvanted Vaccine

Effective mucosal adjuvants enhance the magnitude and quality of the vaccine response. Cyclic di-GMP (CDG) is a promising mucosal vaccine adjuvant. However, its in vivo mechanisms are unclear. Here, we showed, in mice, that CDG elicits stronger Ab and TH responses than the mammalian 2′3′-cyclic GMP-AMP (cGAMP), and generated better protection against Streptococcus pneumoniae infection than 2′3′-cGAMP adjuvanted vaccine. We identified two in vivo mechanisms of CDG. First, intranasally administered CDG greatly enhances Ag uptake, including pinocytosis and receptor-mediated endocytosis in vivo. The enhancement depends on MPYS (STING, MITA) expression in CD11C+ cells. Second, we found that CDG selectively activated pinocytosis-efficient-DCs, leading to TH polarizing cytokines IL-12p70, IFNγ, IL-5, IL-13, IL-23, and IL-6 production in vivo. Notably, CDG induces IFNλ, but not IFNβ, in vivo. Our study revealed previously unrecognized in vivo functions of MPYS and advanced our understanding of CDG as a mucosal vaccine adjuvant.

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Immunomodulatory potential of Chitosan-based materials for cancer therapy: a systematic review of in vitro, in vivo and clinical studies

Biomaterials Science ◽

10.1039/d0bm01984d ◽

2021 ◽

Author(s):

Beatriz Vargas Lima ◽

Maria Oliveira ◽

Mario Adolfo Barbosa ◽

Raquel M. Gonçalves ◽

Flávia Castro

Keyword(s):

Systematic Review ◽

Tumor Microenvironment ◽

Cancer Therapy ◽

Clinical Studies ◽

Vaccine Adjuvant ◽

Immunomodulatory Potential

Chitosan (Ch) has recently been used in different studies as a vaccine adjuvant with ability to modulate the tumor microenvironment (TME). This systematic review aims to elucidate on the added...

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Induction and Differentiation of Dental Epithelium in Vivo and in Vitro

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100053425 ◽

1982 ◽

Vol 40 ◽

pp. 142-145

Author(s):

E. J. Kollar

Keyword(s):

Connective Tissue ◽

Oral Mucosa ◽

Basal Lamina ◽

Functional Derivatives ◽

Specific Source ◽

Dental Epithelium ◽

Connective Tissue Stroma

The differentiation and maintenance of many specialized epithelial structures are dependent on the underlying connective tissue stroma and on an intact basal lamina. These requirements are especially stringent in the development and maintenance of the skin and oral mucosa. The keratinization patterns of thin or thick cornified layers as well as the appearance of specialized functional derivatives such as hair and teeth can be correlated with the specific source of stroma which supports these differentiated expressions.

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Ultrastructural Correlations between Clonal Human Tumor Colonies and in Vivo Neoplasms

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100053711 ◽

1982 ◽

Vol 40 ◽

pp. 210-211

Author(s):

M.J. Murphy ◽

R.R. Price ◽

J.C. Sloman

Keyword(s):

Cultured Cells ◽

Human Tumor ◽

Cell Type ◽

Tumor Mass ◽

Initial Cell ◽

Cloning Assay ◽

Human Tumor Cloning ◽

The Relationship

The in vitro human tumor cloning assay originally described by Salmon and Hamburger has been applied recently to the investigation of differential anti-tumor drug sensitivities over a broad range of human neoplasms. A major problem in the acceptance of this technique has been the question of the relationship between the cultured cells and the original patient tumor, i.e., whether the colonies that develop derive from the neoplasm or from some other cell type within the initial cell population. A study of the ultrastructural morphology of the cultured cells vs. patient tumor has therefore been undertaken to resolve this question. Direct correlation was assured by division of a common tumor mass at surgical resection, one biopsy being fixed for TEM studies, the second being rapidly transported to the laboratory for culture.

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