CpG oligodeoxynucleotides as vaccine adjuvants

2006 ◽  
pp. 73-92 ◽  
Author(s):  
Michael J. McCluskie ◽  
Risini D. Weeratna
Keyword(s):  
Vaccine Adjuvants ◽  
Cpg Oligodeoxynucleotides

scholarly journals ADJUVANTS OF INFLUENZA VACCINES: NEW POSSIBILITIES OF USING SULPHATED POLYSACCHARIDES FROM MARINE BROWN ALGAE

2019 ◽  
Vol 64 (1) ◽  
pp. 5-11
Author(s):  
T. A. Kuznetsova ◽  
E. V. Persiyanova ◽  
T. S. Zaporozhets ◽  
N. N. Besednova
Keyword(s):  
Brown Algae ◽  
Experimental Studies ◽  
Influenza Vaccines ◽  
Sulfated Polysaccharides ◽  
Vaccine Adjuvants ◽  
Mineral Salts ◽  
Scientific Publications ◽  
Cpg Oligodeoxynucleotides ◽  
Advantages And Disadvantages ◽  
Marine Brown Algae

The review article presents the characteristics of the main adjuvant groups (mineral salts of aluminum, synthetic squalene-based adjuvants - MF59 and AS03, CpG-oligodeoxynucleotides, virosomes, polyoxidonium, sovidone) included in the licensed influenza vaccine. The main mechanisms of adjuvant action, advantages and disadvantages of these adjuvants are shown. The vaccines adjuvants in the phase of experimental studies and clinical trials (ISCOMs, Advax™, chitosan) are described too. Particular attention is paid to sulfated polysaccharides (fucoidans) from marine brown algae as vaccine adjuvants. Numerous results of their application in compositions of experimental vaccines are presented. The prospects of sulfated polysaccharides using in the design of influenza vaccines are estimated. These prospects are determined by high biocompatibility, low toxicity and good tolerance of the human body to fucoidans, as well as mechanisms of their adjuvant activity. Sulfated polysaccharides are agonists of toll-like receptors of innate immunity cells and powerful inducers of the cellular and humoral immune response, which is important for the development of influenza vaccines. The review is based on the information presented in the bibliographic and abstract databases of scientific publications, search engines and publishers: RSCI, Web of Science, Scopus, MEDLINE, Google Scholar, PubMed, Springer Nature, Elsevier and others.

Immune Stimulation for the Treatment of Papilloma

2005 ◽  
Vol 114 (9) ◽  
pp. 657-661 ◽  
Author(s):  
David M. Poetker ◽  
Joseph E. Kerschner ◽  
Nalin J. Patel ◽  
Nancy M. Bauman ◽  
Anthony D. Sandler
Keyword(s):  
Therapeutic Effect ◽  
Rabbit Model ◽  
Tumor Burden ◽  
Vaccine Adjuvants ◽  
Bulky Disease ◽  
Curative Therapy ◽  
Cpg Oligodeoxynucleotides ◽  
Cottontail Rabbit ◽  
Cpg Oligodeoxynucleotide ◽  
Immunotherapeutic Strategy

Objectives: There is no curative therapy for recurrent respiratory papillomatosis. Unmethylated dinucleotides of cytosine and guanine (CpG) are potent immune stimulants that have shown efficacy against tumors as monotherapy, as vaccine adjuvants, and in combination with chemotherapies. We examined the therapeutic effect of CpG oligodeoxynucleotides in the treatment of papillomavirus in a cottontail rabbit model (CRPV). Methods: Twenty rabbits were infected with CRPV; 10 were treated with 11 weekly CpG inoculations while treatment control rabbits received intralesional saline solution. Eight rabbits (4 treatment, 4 control) were rechallenged with CRPV 17 weeks after the initial viral challenge and monitored for new papilloma development. Results: Papillomas developed in all 20 rabbits (100%) within 4 weeks of infection. The diagnosis was confirmed histologically. There was no difference in the average tumor burden between the treatment and control groups after 11 weeks of CpG treatments or after 9 additional weeks of observation. There was no difference between the groups in papilloma size at the site of the injections, nor was there eradication of papillomas at remote sites in either group. No new papillomas developed in any of the 8 animals that were rechallenged. Conclusions: We have reproduced an effective mammalian papilloma model for preclinical immunotherapeutic testing. Despite the potency of CpG in triggering host immunity, CpG oligodeoxynucleotide did not show a therapeutic effect against the large papilloma burdens tested in this study. The lack of effect suggests that either enhanced papilloma antigen presentation or targeting of immune-evasive mechanisms used by the papillomas is needed to treat bulky disease with an immunotherapeutic strategy.

scholarly journals Development of Nonaggregating Poly-A Tailed Immunostimulatory A/D Type CpG Oligodeoxynucleotides Applicable for Clinical Use

2015 ◽  
Vol 2015 ◽  
pp. 1-20 ◽  
Author(s):  
Taiki Aoshi ◽  
Yasunari Haseda ◽  
Kouji Kobiyama ◽  
Hirotaka Narita ◽  
Hideaki Sato ◽  
...  
Keyword(s):  
Physical Property ◽  
Good Manufacturing Practice ◽  
Vaccine Adjuvant ◽  
Drug Preparation ◽  
Dependent Manner ◽  
Human Pbmcs ◽  
Vaccine Adjuvants ◽  
Immunostimulatory Activity ◽  
Cpg Oligodeoxynucleotides ◽  
Cpg Odns

Immunostimulatory CpG ODNs have been developed and utilized as TLR9-dependent innate immune activators and vaccine adjuvants. Four different types of immunostimulatory CpG ODNs (A/D, B/K, C, and P type) have been reported. A/D type ODNs are characterized by high IFN-αproduction but intrinsically form aggregates, hindering its good manufacturing practice grade preparation. In this study, we developed several D35-derived ODNs (a commonly used A/D type ODN), which were modified with the addition of a phosphorothioate polynucleotide tail (such as dAs40), and examined their physical properties, solubility in saline, immunostimulatory activity on human PBMCs, and vaccine adjuvant potential in monkeys. We found that two modified ODNs including D35-dAs40 and D35core-dAs40 were immunostimulatory, similar to original D35 in human PBMCs, resulting in high IFN-αsecretion in a dose-dependent manner. Physical property analysis by dynamic light scattering revealed that both D35-dAs40 and D35core-dAs40 did not form aggregates in saline, which is currently impossible for the original D35. Furthermore, D35-dAs40 and D35core-dAs40 worked as better vaccine adjuvant in monkeys. These results suggested that D35-dAs40 and D35core-dAs40 are two promising prototypes of nonaggregating A/D type ODN with advantages of ease of drug preparation for clinical applications as vaccine adjuvants or IFN-αinducing immunomodifiers.

scholarly journals CpG Oligodeoxynucleotides as Vaccine Adjuvants in Primates

2002 ◽  
Vol 168 (4) ◽  
pp. 1659-1663 ◽  
Author(s):  
Daniela Verthelyi ◽  
Richard T. Kenney ◽  
Robert A. Seder ◽  
Albert A. Gam ◽  
Brenda Friedag ◽  
...  
Keyword(s):  
Vaccine Adjuvants ◽  
Cpg Oligodeoxynucleotides

Immunostimulatory CpG Oligodeoxynucleotides as Vaccine Adjuvants

2007 ◽  
pp. 157-174 ◽  
Author(s):  
Dennis M. Klinman ◽  
Debbie Currie ◽  
Hidekazu Shirota
Keyword(s):  
Vaccine Adjuvants ◽  
Cpg Oligodeoxynucleotides

Blood plasmacytoid dendritic cell responses to CpG oligodeoxynucleotides are impaired in human newborns

Blood ◽  
2004 ◽  
Vol 103 (3) ◽  
pp. 1030-1032 ◽  
Author(s):  
Dominique De Wit ◽  
Véronique Olislagers ◽  
Stanislas Goriely ◽  
Françoise Vermeulen ◽  
Hermann Wagner ◽  
...  
Keyword(s):  
Cord Blood ◽  
Plasmacytoid Dendritic Cell ◽  
Interferon Α ◽  
Mrna Levels ◽  
Vaccine Adjuvants ◽  
Bacterial Dna ◽  
Cpg Oligodeoxynucleotides ◽  
Cell Responses ◽  
Hla Dr ◽  
Increased Susceptibility

Abstract Plasmacytoid dendritic cells (pDCs) respond to unmethylated cytosine-phosphate-guanosine (CpG) motifs present in bacterial DNA or unmethylated synthetic oligodeoxynucleotides (CpG). In order to assess the function of pDCs in human newborns, interferon-α (IFN-α) production induced by CpG 2216 and phenotypic maturation of pDCs in response to CpG 2006 were compared in cord blood and adult blood. We first observed that neonatal pDCs displayed decreased up-regulation of CD80, CD83, CD86, and CD40, whereas HLA-DR and CD54 up-regulation did not differ significantly between adults and neonates. We then found that the production of IFN-α in response to CpG was dramatically impaired in cord blood. This neonatal defect was detected both at protein and mRNA levels and was still present in blood of 4-day-old babies. Further experiments on enriched pDCs confirmed that these cells are intrinsically deficient in CpG-induced IFN-α production at birth. These findings might be relevant to the increased susceptibility of human newborns to infections as well as to the use of CpG oligodeoxynucleotides as vaccine adjuvants in the neonatal period. (Blood. 2004;103:1030-1032)

Enzyme-Instructed Self-assembly in Biological Milieu for Theranostics Purpose

2019 ◽  
Vol 26 (8) ◽  
pp. 1351-1365 ◽  
Author(s):  
Zhentao Huang ◽  
Qingxin Yao ◽  
Simin Wei ◽  
Jiali Chen ◽  
Yuan Gao
Keyword(s):  
Small Molecules ◽  
Precision Medicine ◽  
Self Assembly ◽  
Public Healthcare ◽  
Enzymatic Conversion ◽  
Vaccine Adjuvants ◽  
New Paradigm ◽  
Cancer Treatments ◽  
The Past ◽  
Biological Milieu

Precision medicine is in an urgent need for public healthcare. Among the past several decades, the flourishing development in nanotechnology significantly advances the realization of precision nanomedicine. Comparing to well-documented nanoparticlebased strategy, in this review, we focus on the strategy using enzyme instructed selfassembly (EISA) in biological milieu for theranostics purpose. In principle, the design of small molecules for EISA requires two aspects: (1) the substrate of enzyme of interest; and (2) self-assembly potency after enzymatic conversion. This strategy has shown its irreplaceable advantages in nanomedicne, specifically for cancer treatments and Vaccine Adjuvants. Interestingly, all the reported examples rely on only one kind of enzymehydrolase. Therefore, we envision that the application of EISA strategy just begins and will lead to a new paradigm in nanomedicine.

Sign in / Sign up

Export Citation Format

Share Document