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CpG DNA is a potent enhancer of specific immunity in mice immunized with recombinant hepatitis B surface antigen
Journal article   Peer reviewed

CpG DNA is a potent enhancer of specific immunity in mice immunized with recombinant hepatitis B surface antigen

Heather L Davis, Risini Weeratna, Thomas J. Waldschmidt, Lorraine Tygrett, Joachim Schorr and Arthur M Krieg
The Journal of immunology (1950), Vol.160(2), pp.870-876
01/15/1998
DOI: 10.4049/jimmunol.160.2.870
PMID: 9551923

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Abstract

Unmethylated CpG dinucleotides in bacterial DNA or synthetic oligodeoxynucleotides (ODN) cause B cell proliferation and Ig secretion, monocyte cytokine secretion, and activation of NK cell lytic activity and IFN-gamma secretion in vivo and in vitro. The potent immune activation by CpG ODN suggests possible utility for enhancing immune responses to vaccines. Mice immunized with recombinant hepatitis B virus surface Ag and a CpG ODN as an immune enhancer have titers of Abs against HBsAg (anti-HBs) that are five times higher than those of mice immunized with HBsAg and the standard adjuvant, aluminum hydroxide (alum). Ab titers in mice immunized with HBsAg and both CpG ODN plus alum were 35 times higher than the titers in mice immunized with alum alone, indicating a strong synergistic interaction between the CpG ODN and alum. ODN without CpG motifs had little or no immune-enhancing activity at the doses used herein. Alum induces a Th2 humoral response (mostly IgG1) and no CTL. In contrast, CpG ODN gives a strong Thl response with predominantly IgG2a Abs and CTL, even when mixed with alum. In vitro studies to determine possible mechanisms of CpG immune-enhancing effects show that CpG ODN induce expression of costimulatory molecules on Ag-presenting cells and drive B cell isotype switching in the appropriate cytokine milieu. These studies demonstrate that CpG ODN are promising new immune enhancers for vaccination applications.
Hepatitis B Surface Antigens - genetics Vaccines, DNA - genetics Oligodeoxyribonucleotides - administration & dosage Adjuvants, Immunologic - administration & dosage Vaccines, DNA - immunology Th1 Cells - immunology Vaccines, DNA - administration & dosage Hepatitis B Surface Antigens - administration & dosage Th1 Cells - metabolism Immunoglobulin G - biosynthesis Oligodeoxyribonucleotides - genetics Adjuvants, Immunologic - genetics Female Immunoglobulin Class Switching - drug effects Cytotoxicity, Immunologic - drug effects B-Lymphocytes - metabolism CpG Islands - immunology Oligodeoxyribonucleotides - immunology Cells, Cultured Hepatitis B Surface Antigens - immunology Recombinant Proteins - genetics Alum Compounds - pharmacology Recombinant Proteins - administration & dosage Animals B-Lymphocytes - immunology Recombinant Proteins - immunology Lymphocyte Activation - drug effects Mice Mice, Inbred BALB C

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