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

Abstract

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.

A CpG oligodeoxynucleotide potentiates the anti-tumor effect of HSP65-Her2 fusion protein against Her2 positive B16 melanoma in mice

“…Our previous data showed that BW006 stimulated human PBMCs and mouse spleen cells to proliferate and to express CD69 and CD80 [17,18], and activated rat white blood cells to upregulate CD40 and CD86 [16]. The properties may contribute to the enhanced presentation of HSP65-Her2 to generate specific CTL against Her2 + B16 melanoma.…”

Initial preclinical safety of non‐replicating human endogenous retrovirus envelope protein‐coated baculovirus vector‐based vaccines against human papillomavirus

“…Whereas ALT and AST are liver toxicity biomarkers, BUN and creatinine are well‐known biomarkers of kidney toxicity (Liu et al ., ). Here, we observed no significant changes in BUN (Fig.…”

Cpg 684: An Effective Adjuvant for the Inactivated COVID-19 Vaccine in Mice

“…CpG ODNs improve the activation and inhibits apoptosis of B cells, enhances the IgG subclass switch and induces the maturation and differentiation of dendritic cells [ 16–20 ]. The CpG 1018 adjuvant hepatitis B vaccine manufactured by Dynavax has been approved by US FDA for marketing in 2017 [ 21 ], and CpG 684 has proved its adjuvant effect in hepatitis B vaccines [ 22 ]. To increase the immune response to the inactivated COVID-19 vaccine, this study investigates the potential for CpG 684 as an adjuvant.…”