Adjuvant effect of polyadenylic.Polyuridylic acid on antibody production of recombinant hepatitis B surface antigen in mice

Park, Soo‐Jin; Kim, Jae Hak; Han, Kwang Hyub; Chon, Chae Yoon; Hahm, Ki Baik; Moon, Young Myoung; Kang, Jin Kyung; Park, In Suh; Youn, Jung Koo

doi:10.1016/0192-0561(95)00031-v

Cited by 5 publications

(2 citation statements)

References 15 publications

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“…For example, (dG, dC) activates natural killer cells, IFN‒ γ production, and B cell proliferation and immunoglobulin secretion1, 2. Polyadenylic polyuridylic acid has been reported to have adjuvant properties and has been used in several clinical trials3–5. Aside from these artificial polynucleotides, bacterial genomic DNA was reported to activate NK cells and induce tumor regression in mouse cancer models but vertebrate DNA was found to be immunologically inactive6–8.…”

Section: Identification Of Cpg‒s Dna As An Immune Stimulatory Polyanionmentioning

confidence: 99%

Direct Immunologic activities of CpG DNA and implications for gene therapy

Krieg¹

1999

J. Gene Med.

101

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Vertebrate immune systems have evolved the ability to detect and be activated by most microbial and viral DNAs by virtue of their content of unmethylated ‘CpG motifs’, which are selectively suppressed in vertebrate DNA. Because their CpGs are also unmethylated, the DNA in gene therapy vectors routinely induces direct immune stimulation through activating this host defense mechanism. Administration of such ‘CpG DNA’ by injection or inhalation triggers rapid activation of B cells, monocytes, macrophages, dendritic cells, and natural killer cells, along with the release of pro‐inflammatory cytokines. These immune stimulatory effects can be prevented by chloroquine and other drugs that interfere with endosomal maturation or by the presence of certain neutralizing DNA sequences, which block the immune stimulatory CpG motifs. Aside from serving as the genetic code, DNA can have direct immune activities. Vertebrate immune systems have evolved a defense mechanism that is able to broadly detect most microbial and viral DNAs because of differences in the frequency and methylation of CpG dinucleotides in particular base contexts. B cells, monocytes, macrophages, and dendritic cells spontaneously take up DNA of any type. If the DNA contains these immune stimulatory ‘CpG‐S motifs’, the cells become activated within minutes and begin producing pro‐inflammatory cytokines such as IL‐6 and IL‐12 and upregulate expression of co‐stimulatory molecules. This results in the activation of both innate and acquired immune responses. The pro‐inflammatory effects of CpG‐S motifs are opposed by CpG dinucleotides in certain distinct base contexts, termed neutralizing or CpG‐N motifs. Increasing the ratio of CpG‐S to CpG‐N motifs enhances the immune stimulatory effects of DNA, even if the total level of CpGs in the DNA is not altered. While this is useful in generating enhanced genetic vaccines, the opposite strategy is likely to become useful for the generation of gene therapy vectors with reduced inflammatory effects. Copyright © 1999 John Wiley & Sons, Ltd.

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Section: Identification Of Cpg‒s Dna As An Immune Stimulatory Polyanionmentioning

confidence: 99%

Direct Immunologic activities of CpG DNA and implications for gene therapy

Krieg¹

1999

J. Gene Med.

101

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“…Although it has some similar properties to poly(rI 7 rC) in terms of its ability to promote production of IFNs and activate NK cells, poly(A 7 U) has been proposed to be less toxic. Poly(A 7 U) has also been shown to have adjuvant effects when administered in combination with hepatitis B surface antigen to mice [23]. In human clinical trials, poly(A 7 U) has shown some encouraging signs of efficacy in patients with breast cancer [24,25].…”

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confidence: 99%