Chemical Synthesis, Versatile Structures and Functions of Tailorable Adjuvants for Optimizing Oral Vaccination

Zhang, Lei; Hu, Chaohua; Yang, Wendi; Liu, Xiaolin; Wu, Yunkun

doi:10.1021/acsami.6b10470

Cited by 12 publications

(7 citation statements)

References 141 publications

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“…Recent results suggest that hydrophilic polyester-based nanoparticles in combination with a TLR3 ligand can efficiently act as an adjuvant and induce the strong T-cell response of a peptide antigen derived from human papillomavirus (7). Thus, there is a demand for new adjuvants with versatile functions like intelligent release and biocompatibility with the immune system to enhance the vaccination (40).…”

Section: Discussionmentioning

confidence: 99%

A TLR4-derived non-cytotoxic, self-assembling peptide functions as a vaccine adjuvant in mice

Tandon

Pathak

Harioudh

et al. 2018

Journal of Biological Chemistry

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Vaccination is devised/formulated to stimulate specific and prolonged immune responses for long-term protection against infection or disease. A vaccine component, namely adjuvant, enhances antigen recognition by the host immune system and thereby stimulates its cellular and adaptive responses. Especially synthetic Toll-like receptor (TLR) agonists having selfassembling properties are considered as good candidates for adjuvant development. Here, a human TLR4-derived 20-residue peptide (TR-433), present in the dimerization interface of the TLR4 -myeloid differentiation protein-2 (MD2) complex, displayed self-assembly and adopted a nanostructure. Both in vitro studies and in vivo experiments in mice indicated that TR-433 is nontoxic. TR-433 induced pro-inflammatory responses in THP-1 monocytes and HEK293T cells that were transiently transfected with TLR4/CD14/MD2 and also in BALB/c mice. In light of the self-assembly and pro-inflammatory properties of TR-433, we immunized with a mixture of TR-433 and either ovalbumin or filarial antigen trehalose-6-phosphate phosphatase (TPP). A significant amount of IgG titers was produced, suggesting adjuvanting capability of TR-433 that was comparable with that of Freund's complete adjuvant (FCA) and appreciably higher than that of alum. We found that TR-433 preferentially activates type 1 helper T cell (T h 1) response rather than type 2 helper T cell (T h 2) response. To our knowledge, this is the first report on the identification of a short TLR4-derived peptide that possesses both self-assembling and pro-inflammatory properties and has significant efficacy as an adjuvant, capable of activating cellular responses in mice. These results indicate that TR-433 possesses significant potential for development as a new adjuvant in therapeutic application. 2 The abbreviations used are: FCA, Freund's complete adjuvant; FIA, Freund's incomplete adjuvant; TLR, Toll-like receptor; LPS, lipopolysaccharide; TPP, trehalose-6-phosphate phosphatase; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; TEM, transmission EM; ThT, thioflavin T; TNF, tumor necrosis factor; IL, interleukin; PMA, phorbol 12-myristate 13-acetate; Ova, ovalbumin; HRP, horseradish peroxidase; IFN, interferon. Figure 8. TR-433 adjuvant activity depends on T-bet expression. mRNA expressions of T-bet and GATA-3 were analyzed in splenocytes in duplicates in two independent experiments (n ϭ 2). Mouse glyceraldehyde-3-phosphate dehydrogenase was used as an endogenous control, and relative -fold change was determined by the comparative ⌬CT method. Statistical analysis was carried out using one-way analysis of variance using Dunnett's test.

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Section: Discussionmentioning

confidence: 99%

A TLR4-derived non-cytotoxic, self-assembling peptide functions as a vaccine adjuvant in mice

Tandon

Pathak

Harioudh

et al. 2018

Journal of Biological Chemistry

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“…Alginate-coated chitosan microparticles could protect acid-labile drugs effectively from degradation in acidic pH than chitosan microparticles alone ( Li et al, 2017 ) and enhanced antigen uptake by mucosal lymphoid tissues, especially at the Peyer`s patches ( Zhang et al, 2016 ). Liu et al (2013) showed alginate-coated chitosan NPs could be efficient and was observed to be safe carriers for the oral delivery of legumain DNA vaccines ( Liu et al, 2013 ).…”

Section: Polymeric Npsmentioning

confidence: 99%

Nano and Microparticles as Potential Oral Vaccine Carriers and Adjuvants Against Infectious Diseases

Jazayeri¹,

Lim²,

Shameli

et al. 2021

Front. Pharmacol.

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Mucosal surfaces are the first site of infection for most infectious diseases and oral vaccination can provide protection as the first line of defense. Unlike systemic administration, oral immunization can stimulate cellular and humoral immune responses at both systemic and mucosal levels to induce broad-spectrum and long-lasting immunity. Therefore, to design a successful vaccine, it is essential to stimulate the mucosal as well as systemic immune responses. Successful oral vaccines need to overcome the harsh gastrointestinal environment such as the extremely low pH, proteolytic enzymes, bile salts as well as low permeability and the low immunogenicity of vaccines. In recent years, several delivery systems and adjuvants have been developed for improving oral vaccine delivery and immunogenicity. Formulation of vaccines with nanoparticles and microparticles have been shown to improve antigen stability, availability and adjuvanticity as well as immunostimulatory capacity, target delivery and specific release. This review discusses how nanoparticles (NPs) and microparticles (MPs) as oral carriers with adjuvant characteristics can be beneficial in oral vaccine development.

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“…Immunity via oral administration has proven to be widely applicable, efficient in time and cost, and greatly applicable to the safety management of fish of various sizes and stages (31)(32)(33). In this study, MSN was used to deliver antigen to prepare a highload, pH controlled release, oral nanovaccine, which could reach the intestinal tract under the protection of enteric coatings, HP55, and directly pass through the intestinal epithelial cells to deliver antigen to Peyer patches, thereby interacting with immune cells to promote the induction of specific immune responses (34,35). We analyzed the serum antibody levels of immunized large yellow croaker and the expression levels of IFNg, IL-1b, IL-2, IL-4, and IL-13 in intestine, spleen, and head kidney.…”

Section: Discussionmentioning

confidence: 99%

pH-Controlled Release of Antigens Using Mesoporous Silica Nanoparticles Delivery System for Developing a Fish Oral Vaccine

et al. 2021

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The development of effective vaccines and delivery systems in aquaculture is a long-term challenge for controlling emerging and reemerging infections. Cost-efficient and advanced nanoparticle vaccines are of tremendous applicability in prevention of infectious diseases of fish. In this study, dihydrolipoamide dehydrogenase (DLDH) antigens of Vibrio alginolyticus were loaded into mesoporous silica nanoparticles (MSN) to compose the vaccine delivery system. Hydroxypropyl methylcellulose phthalate (HP55) was coated to provide protection of immunogen. The morphology, loading capacity, acid-base triggered release were characterized and the toxicity of nanoparticle vaccine was determined in vitro. Further, the vaccine immune effects were evaluated in large yellow croaker via oral administration. In vitro studies confirmed that the antigen could be stable in enzymes-rich artificial gastric fluid and released under artificial intestinal fluid environment. In vitro cytotoxicity assessment demonstrated the vaccines within 120 μg/ml have good biocompatibility for large yellow croaker kidney cells. Our data confirmed that the nanoparticle vaccine in vivo could elicit innate and adaptive immune response, and provide good protection against Vibrio alginolyticus challenge. The MSN delivery system prepared may be a potential candidate carrier for fish vaccine via oral administration feeding. Further, we provide theoretical basis for developing convenient, high-performance, and cost-efficient vaccine against infectious diseases in aquaculture.

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Chemical Synthesis, Versatile Structures and Functions of Tailorable Adjuvants for Optimizing Oral Vaccination

Cited by 12 publications

References 141 publications

A TLR4-derived non-cytotoxic, self-assembling peptide functions as a vaccine adjuvant in mice

A TLR4-derived non-cytotoxic, self-assembling peptide functions as a vaccine adjuvant in mice

Nano and Microparticles as Potential Oral Vaccine Carriers and Adjuvants Against Infectious Diseases

pH-Controlled Release of Antigens Using Mesoporous Silica Nanoparticles Delivery System for Developing a Fish Oral Vaccine

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