CpG DNA as a vaccine adjuvant - PubMed (original) (raw)

Review

CpG DNA as a vaccine adjuvant

Christian Bode et al. Expert Rev Vaccines. 2011 Apr.

Abstract

Synthetic oligodeoxynucleotides (ODNs) containing unmethylated CpG motifs trigger cells that express Toll-like receptor 9 (including human plasmacytoid dendritic cells and B cells) to mount an innate immune response characterized by the production of Th1 and proinflammatory cytokines. When used as vaccine adjuvants, CpG ODNs improve the function of professional antigen-presenting cells and boost the generation of humoral and cellular vaccine-specific immune responses. These effects are optimized by maintaining ODNs and vaccine in close proximity. The adjuvant properties of CpG ODNs are observed when administered either systemically or mucosally, and persist in immunocompromised hosts. Preclinical studies indicate that CpG ODNs improve the activity of vaccines targeting infectious diseases and cancer. Clinical trials demonstrate that CpG ODNs have a good safety profile and increase the immunogenicity of coadministered vaccines.

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Figures

Figure 1. Time course of CpG-mediated gene regulation in vivo

Mice were injected intraperitoneally with 400 µg of CpG ODN. Gene expression in the spleen was monitored over time by microarray. At least four biological replicates were analyzed independently at each time point in at least two independent experiments. Differentially regulated genes were identified by comparison to untreated mice (n = 6) using a stringency cutoff of p < 0.00001. Ingenuity Pathway Analysis was used to identify those genes differentially regulated during this period based on their function and role in signaling pathways. ODN: Oligodeoxynucleotide.

Figure 2. Mechanism by which CpG oligodeoxynucleotides facilitate innate and adaptive immune responses

CpG ODNs directly activate pDCs and B cells. The resultant immune response is characterized by the production of proinflammatory and Th1 cytokines and polyreactive immunoglobulin. This innate immune response forms a foundation on which antigen-specific adaptive immunity is based. By improving the function of professional APCs, CpG ODNs facilitate the generation of humoral and cellular adaptive immune responses against coadministered vaccine antigens. APC: Antigen-presenting cell; CTL: Cytotoxic T lymphocyte; ODN: Oligodeoxynucleotide; pDC: Plasmacytoid dendritic cell; TNF: Tumor necrosis factor.

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Website

1. Phase I study of the safety and immunogenicity of BSAM-2/ alhydrogel(registered trademark)+CPG 7909, an asexual blood stage vaccine for Plasmodium falciparum malaria in adults in the US and Mali. http://clinicaltrials.gov/ct2/show/NCT00889616.

CpG DNA as a vaccine adjuvant - PubMed (original) (raw)