Clinical evaluation of CpG oligonucleotides as adjuvants for vaccines targeting infectious diseases and cancer

Scheiermann, Julia; Klinman, Dennis M.

doi:10.1016/j.vaccine.2014.06.065

Cited by 281 publications

(265 citation statements)

References 136 publications

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“…Because aluminum salts cannot be administered intradermally due to local adverse effects, adjuvants CpG and CT were assessed for intradermal IPV1 immunization. Both CpG and CT have shown to be safe as adjuvant in intradermal immunization in humans (36,37). In the present study, immuneenhancing effects on IPV1-specific IgG responses by the adjuvants CpG and CT were significant, which indicates that CpG and CT might be potential adjuvant candidates for intradermal IPV1 immunization and may lead to dose sparing.…”

Section: Discussionsupporting

confidence: 54%

Determination of Depth-Dependent Intradermal Immunogenicity of Adjuvanted Inactivated Polio Vaccine Delivered by Microinjections via Hollow Microneedles

et al. 2016

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Purpose The aim of this study was to investigate the depthdependent intradermal immunogenicity of inactivated polio vaccine (IPV) delivered by depth-controlled microinjections via hollow microneedles (HMN) and to investigate antibody response enhancing effects of IPV immunization adjuvanted with CpG oligodeoxynucleotide 1826 (CpG) or cholera toxin (CT). Methods A novel applicator for HMN was designed to permit depth-and volume-controlled microinjections. The applicator was used to immunize rats intradermally with monovalent IPV serotype 1 (IPV1) at injection depths ranging from 50 to 550 μm, or at 400 μm for CpG and CT adjuvanted immunization, which were compared to intramuscular immunization. Results The applicator allowed accurate microinjections into rat skin at predetermined injection depths (50-900 μm), -volumes (1-100 μL) and -rates (up to 60 μL/min) with minimal volume loss (±1-2%). HMN-mediated intradermal immunization resulted in similar IgG and virus-neutralizing antibody titers as conventional intramuscular immunization. No differences in IgG titers were observed as function of injection depth, however IgG titers were significantly increased in the CpG and CT adjuvanted groups (7-fold).Conclusion Intradermal immunogenicity of IPV1 was not affected by injection depth. CpG and CT were potent adjuvants for both intradermal and intramuscular immunization, allowing effective vaccination upon a minimally-invasive single intradermal microinjection by HMN.

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Section: Discussionsupporting

confidence: 54%

Determination of Depth-Dependent Intradermal Immunogenicity of Adjuvanted Inactivated Polio Vaccine Delivered by Microinjections via Hollow Microneedles

et al. 2016

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“…nanoparticle | vaccine platform | replicon | viruses | parasites T oday, there are a range of vaccine technologies used clinically, with varied use of inactivated pathogens, molecular antigens, adjuvants, delivery technologies, administration routes, and dosing regimes (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13). Although existing vaccine systems have had a huge impact on prevention of infectious disease, challenges remain.…”

mentioning

confidence: 99%

Dendrimer-RNA nanoparticles generate protective immunity against lethal Ebola, H1N1 influenza, and Toxoplasma gondii challenges with a single dose

Chahal

Khan

Cooper

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

337

260

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Vaccines have had broad medical impact, but existing vaccine technologies and production methods are limited in their ability to respond rapidly to evolving and emerging pathogens, or sudden outbreaks. Here, we develop a rapid-response, fully synthetic, single-dose, adjuvant-free dendrimer nanoparticle vaccine platform wherein antigens are encoded by encapsulated mRNA replicons. To our knowledge, this system is the first capable of generating protective immunity against a broad spectrum of lethal pathogen challenges, including H1N1 influenza, Toxoplasma gondii, and Ebola virus. The vaccine can be formed with multiple antigen-expressing replicons, and is capable of eliciting both CD8+ T-cell and antibody responses. The ability to generate viable, contaminant-free vaccines within days, to single or multiple antigens, may have broad utility for a range of diseases.

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“…in REF. 54). Therefore, CpG-ODNs may eventually reach the clinic as adjuvants for prophylactic vaccines, rather than in the far more demanding context of therapeutic immunizations against tumours.…”

Section: Biomarkersmentioning

confidence: 99%

Translating nucleic acid-sensing pathways into therapies

2015

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Nucleic acid sensing by innate receptors initiates immune defences against viruses and other pathogens. A hallmark of this response is the release of interferons (IFNs), which promote protective immunity by inducing IFN-stimulated genes (ISGs). A similar ISG signature is found in autoinflammatory and autoimmune conditions, indicating that chronic activation of nucleic acid-sensing pathways may contribute to these diseases. Here, we review how nucleic acid-sensing pathways are currently being targeted pharmacologically with both agonists and antagonists. We discuss how an improved understanding of the biology of these pathways is leading to novel therapies for infections, cancer, and autoimmune and autoinflammatory disorders, and how new therapeutics will, in turn, generate a deeper understanding of these complex diseases.

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Clinical evaluation of CpG oligonucleotides as adjuvants for vaccines targeting infectious diseases and cancer

Cited by 281 publications

References 136 publications

Determination of Depth-Dependent Intradermal Immunogenicity of Adjuvanted Inactivated Polio Vaccine Delivered by Microinjections via Hollow Microneedles

Determination of Depth-Dependent Intradermal Immunogenicity of Adjuvanted Inactivated Polio Vaccine Delivered by Microinjections via Hollow Microneedles

Dendrimer-RNA nanoparticles generate protective immunity against lethal Ebola, H1N1 influenza, and Toxoplasma gondii challenges with a single dose

Translating nucleic acid-sensing pathways into therapies

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