Synthetic Oligodeoxynucleotides Induce Gastritis in Mice

Yamamoto, Go; Kobayashi, Hiroko; Hikichi, Takuto; Irisawa, Atsushi; Obara, Katsutoshi; Ohira, Hiromasa

doi:10.5387/fms.55.23

Cited by 4 publications

(4 citation statements)

References 24 publications

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“…Single intraperitoneal injection of 300 µg per dam CpG ODN to pregnant C57BL/6 mice resulted in increased fetal resorptions and craniofacial/limb defects (Prater et al , ). Synthetic CpG ODN induced gastritis in mice (Yamamoto et al , ). CpG ODN induced early hepatic injury, but mediated long‐term protection against lipopolysaccharide‐mediated hepatotoxicity in SD rats (Slotta et al , ).…”

Section: Discussionmentioning

confidence: 99%

“…As an agonist of toll‐like receptor‐9 (TLR9; Tsujimoto et al , ), CpG ODN activates TLR9 expressing immune cells including plasmacytoid dendritic cells (PDC), macrophages, B cells and monocytes (Heikenwalder et al , ; Krieg, ), promoting a Th1‐biased immune response (Sugai et al , ). CpG ODN can upregulate the TLR9 mRNA expression in activated B‐cells and upregulate the mRNA expression of some Th1‐promoting cytokines such as interleukin 6, interleukin 12 and interferon‐ γ (IFN‐ γ ) (Cognasse et al , ; Tada et al , ; Yamamoto et al , ). Different species may have different TLR9 expression profiles.…”

Section: Introductionmentioning

confidence: 99%

“…To develop CpG ODN as novel adjuvant of human use, a prerequisite is to investigate its safety. Although there have been some reports on the safety of CpG ODN (Heikenwalder et al , ; Prater et al , ; Krieg, ; Yamamoto et al , ), the safety profile of CpG ODN has still not been fully clarified, and little has been reported about the systematic and comprehensive safety evaluation on repeated CpG ODN administration. We performed a comprehensive 28‐day repeated dose toxicity study of a new adjuvant CpG 684 in rats to evaluate the potential toxicity.…”

Section: Introductionmentioning

confidence: 99%

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A safety study of a B‐class CpG ODN in Sprague–Dawley rats

Liu

Shen

Liu

et al. 2011

J of Applied Toxicology

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Oligodeoxynucleotides containing CpG motifs (CpG ODNs) are potent immune activators and are being tested as anti-tumor, antimicrobial agents and as adjuvants in vaccines. Little has been reported, however, about the systematic and comprehensive safety evaluation on repeated CpG ODN administration. To investigate the safety profile of a newly developed CpG ODN, CpG 684, we conducted a 28-day repeated dose toxicity study in rats, at dose levels of 5, 20 and 150 µg CpG 684 per rat. No abnormalities in clinical observations, growth, urinalysis and bone marrow cell counts were found in CpG 684 treated rats. CpG 684 was proved biologically active, capable of up-regulating the expressions of CD40 and CD86 molecules. The monocyte numbers were increased at the dose levels of 20 and 150 µg per rat. The spleen weights were increased in female rats at the dose level of 150 µg per rat. Microscopically, 5, 20 and 150 µg per rat CpG 684 caused local inflammatory cell infiltration and hyperplasia of fibrous tissue at injection sites; the treatment of 5 and 150 µg per rat CpG 684 induced enhanced inflammatory reaction in inguinal lymphoid tissue, and the dose of 150 µg per rat induced cell hyperplasia in white pulp of spleen and white pulp expansion. CpG 684 at 150 µg per rat led to decreases in peripheral lymphocyte, serum globulin, glucose, alkaline phosphatase and K+ levels in female rats, and induced the decrease in serum albumin and total protein in rats of both sexes. The data from this study will provide an important reference for developing CpG 684 as an adjuvant for vaccines of human use.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A safety study of a B‐class CpG ODN in Sprague–Dawley rats

Liu

Shen

Liu

et al. 2011

J of Applied Toxicology

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“…Oligodeoxynucleotides containing CpG motifs (CpG ODNs), which consist of a central unmethylated CG dimer present at a high frequency in bacterial and viral DNA, is recognized by mammalian Toll-like receptor (TLR) 9 and induces Th1 immune responses [ 27 ]. Although CpG ODNs have been approved by the FDA for use in a hepatitis B subunit vaccine as an adjuvant, doses up to 3 mg per injection increase not only costs but also the risk of side effects that are attributed to the systemic diffusion of this proinflammatory material [ 28 , 29 , 30 ]. In our previous reports, we proved that encapsulation of CpG ODNs into nanoparticles, including ionizable lipid nanoparticles (LNPs) that were proved to show adjuvant effects for protein subunit vaccines and approved by the FDA as vectors for coronavirus disease 2019 (COVID-19) mRNA vaccines, showed excellent efficacy in enhancing the antigen-specific CMI responses induced by subunit vaccines with dose sparing [ 31 , 32 , 33 , 34 , 35 ].…”

Section: Introductionmentioning

confidence: 99%

Ionizable Lipid Nanoparticles Enhanced the Synergistic Adjuvant Effect of CpG ODNs and QS21 in a Varicella Zoster Virus Glycoprotein E Subunit Vaccine

et al. 2022

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Varicella zoster virus (VZV) causes two diseases: varicella upon primary infection and herpes zoster when latent viruses in the sensory ganglia reactivate. While varicella vaccines depend on humoral immunity to prevent VZV infection, cell-mediated immunity (CMI), which plays a therapeutic role in the control or elimination of reactivated VZV in infected cells, is decisive for zoster vaccine efficacy. As one of the most abundant glycoproteins of VZV, conserved glycoprotein E (gE) is essential for viral replication and transmission between ganglion cells, thus making it an ideal target subunit vaccine antigen; gE has been successfully used in the herpes zoster vaccine ShingrixTM on the market. In this report, we found that ionizable lipid nanoparticles (LNPs) approved by the Food and Drug Administration (FDA) as vectors for coronavirus disease 2019 (COVID-19) mRNA vaccines could enhance the synergistic adjuvant effect of CpG oligodeoxynucleotides (CpG ODNs) and QS21 on VZV-gE, affecting both humoral immunity and CMI. Vaccines made with these LNPs showed promise as varicella vaccines without a potential risk of herpes zoster, which identifies them as a novel type of herpes zoster vaccine similar to ShingrixTM. All of the components in this LNP-CpG-QS21 adjuvant system were proven to be safe after mass vaccination, and the high proportion of cholesterol contained in the LNPs was helpful for limiting the cytotoxicity induced by QS21, which may lead to the development of a novel herpes zoster subunit vaccine for clinical application.

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