Biphasic Lipid Vesicles as a Subcutaneous Delivery System for Protein Antigens and CpG Oligonucleotides

Alcon, Valeria; Baca-Estrada, Maria E.; Potter, Andrew; Babiuk, Lorne A.; Kumar, Praveen; Földvári, Marianna

doi:10.2174/156720106776359212

Cited by 3 publications

(2 citation statements)

References 19 publications

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“…For example, biphasic lipid vesicles have been proposed for the delivery of oligo/polynucleotides (58). The demonstration that the c-di-GMP acted as an adjuvant for vaccination with S. aureus ClfA Ag when coinjected i.m.…”

Section: Discussionmentioning

confidence: 99%

Bacterial c-di-GMP Is an Immunostimulatory Molecule

Karaolis

Means

Yang

et al. 2007

The Journal of Immunology

203

239

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Cyclic diguanylate (c-di-GMP) is a bacterial intracellular signaling molecule. We have shown that treatment with exogenous c-di-GMP inhibits Staphylococcus aureus infection in a mouse model. We now report that c-di-GMP is an immodulator and immunostimulatory molecule. Intramammary treatment of mice with c-di-GMP 12 and 6 h before S. aureus challenge gave a protective effect and a 10,000-fold reduction in CFUs in tissues (p < 0.001). Intramuscular vaccination of mice with c-di-GMP coinjected with S. aureus clumping factor A (ClfA) Ag produced serum with significantly higher anti-ClfA IgG Ab titers (p < 0.001) compared with ClfA alone. Intraperitoneal injection of mice with c-di-GMP activated monocyte and granulocyte recruitment. Human immature dendritic cells (DCs) cultured in the presence of c-di-GMP showed increased expression of costimulatory molecules CD80/CD86 and maturation marker CD83, increased MHC class II and cytokines and chemokines such as IL-12, IFN-γ, IL-8, MCP-1, IFN-γ-inducible protein 10, and RANTES, and altered expression of chemokine receptors including CCR1, CCR7, and CXCR4. c-di-GMP-matured DCs demonstrated enhanced T cell stimulatory activity. c-di-GMP activated p38 MAPK in human DCs and ERK phosphorylation in human macrophages. c-di-GMP is stable in human serum. We propose that cyclic dinucleotides like c-di-GMP can be used clinically in humans and animals as an immunomodulator, immune enhancer, immunotherapeutic, immunoprophylactic, or vaccine adjuvant.

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Section: Discussionmentioning

confidence: 99%

Bacterial c-di-GMP Is an Immunostimulatory Molecule

Karaolis

Means

Yang

et al. 2007

The Journal of Immunology

203

239

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“…In other applications, causing irritation or physical injury to the skin is counterproductive and an effective noninvasive topical delivery system would be needed. Biphasic vesicles [214][215][216] and gemini nanoparticles (Figure 7) [9,172] were shown to effectively deliver plasmid DNA into intact human or mouse skin in vitro and in vivo. [217].…”

Section: In Vitro Versus In Vivo Deliverymentioning

confidence: 99%

Advancing Nonviral Gene Delivery: Lipid- and Surfactant-Based Nanoparticle Design Strategies

et al. 2010

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Gene therapy is a technique utilized to treat diseases caused by missing, defective or overexpressing genes. Although viral vectors transfect cells efficiently, risks associated with their use limit their clinical applications. Nonviral delivery systems are safer, easier to manufacture, more versatile and cost effective. However, their transfection efficiency lags behind that of viral vectors. Many groups have dedicated considerable effort to improve the efficiency of nonviral gene delivery systems and are investigating complexes composed of DNA and soft materials such as lipids, polymers, peptides, dendrimers and gemini surfactants. The bottom-up approach in the design of these nanoparticles combines components essential for high levels of transfection, biocompatibility and tissue-targeting ability. This article provides an overview of the strategies employed to improve in vitro and in vivo transfection, focusing on the use of cationic lipids and surfactants as building blocks for nonviral gene delivery systems.

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