Repeated Administration of Synthetic Oligodeoxynucleotides Expressing CpG Motifs Provides Long-Term Protection against Bacterial Infection

Abstract

Synthetic oligodeoxynucleotides (ODN) expressing unmethylated CpG motifs stimulate an innate immune response characterized by the production of polyreactive immunoglobulin M antibodies and immunomodulatory cytokines. This immune response has been shown to protect mice from challenge by Listeria monocytogenes andFrancisella tularensis for up to 2 weeks. By repeatedly administering CpG ODN two to four times/month, we found that this protection could be maintained indefinitely. Protection was associated with a significant increase in the number of spleen cells that could be triggered by subsequent pathogen exposure to secrete gamma interferon and interleukin-6 in vivo (P < 0.01). ODN-treated animals remained healthy and developed neither macroscopic nor microscopic evidence of tissue damage or inflammation. Thus, repeated administration of CpG ODN may provide a safe means of conferring long-term protection against infectious pathogens.

Characteristics of oligodeoxyribonucleotides that induce interferon (IFN)-α in the pig and the phenotype of the IFN-α producing cells

“…However, the IFN-a inducing capacity was partly retained after inversion of the CpG to GpC in ODN H and ODN I which is in line with previous results using human PBMC (Magnusson et al, 2001b). It is in this context noteworthy that, after inversion of the CpGs to GpC, the ODN A2 retained its ability to enhance ovalbumin specific antibody production and cell proliferation when injected in pigs ( Van der Stede et al, 2002), but not its protective effect at challenge with Listeria monocytogenes in mice (Klinman et al, 1999). Thus, the importance of CpG motifs may differ for immune parameter studied.…”

“…TAG CGTKlinman et al (1996Klinman et al ( , 1999, Van der Stede et al (2002) A2 GC GCT AGA GCT TAG GCT Van der Stede et al (2002) 2216 ggG GGA CGA TCG TCg ggg gG Jarrossay et al (2001), Krug et al (2001a) 2216diester GGG GGA CGA TCG TCG GGG GG New modification of 2216 D19diester (D25) GGT GCA TCG ATG CAG GGG GG Kamstrup et al (2001) D19 ggT GCA TCG ATG CAG ggg gg Verthelyi et al (2001) MM1…”

The use of nanolipoprotein particles to enhance the immunostimulatory properties of innate immune agonists against lethal influenza challenge

“…what may otherwise be considered a lethal infection. There is precedent for targeting innate immunity as a prophylactic countermeasure against biothreat agents, as CpG has previously been shown to be protective in mice against Francisella tularensis and Burkholderia pseudomallei [17,24,25], and synthetic TLR4 agonists have been shown to be protective in mice against F. tularensis and Y. pestis [13e15]. However, the protection afforded in these studies was variable, with some demonstrating only marginally better survival than untreated control animals.…”

The immunoreactivity of a chimeric multi-epitope DNA vaccine against IBV in chickens

“…In this study we constructed the GA/GP as spacer between two epitopes which not only minimized junctional epitopes, but also simultaneously optimized for proteosome processing. Secondly, CpG motif in plasmid as well as CpG oligodeoxynucleotides (ODN) can activate systemic and mucosal immune responses, induce lymphocytes and macrophages to secrete polyreactive antibodies and/or cytokines, and induce proliferation of B-cell [24][25][26][27]. We inserted CpG motif in the multi-epitope chimeric gene to enhance immune response.…”