Use of CpG oligodeoxynucleotides as immunoprotective agents

Abstract

Single-stranded oligodeoxynucleotides (ODNs) synthesised to express unmethylated 'CpG motifs' mimic the ability of bacterial DNA to trigger the innate immune system. CpG ODNs stimulate cells that express Toll-like receptor 9, initiating an immunomodulatory cascade resulting in the activation of B and T lymphocytes, natural killer cells, monocytes, macrophages and dendritic cells. CpG ODNs improve the host's ability to resist infection by accelerating and improving the induction of an innate and then adaptive immune response, characterised by the production of Th1 and pro-inflammatory cytokines, chemokines and polyreactive antibodies. Studies in rodents and non-human primates demonstrate that CpG ODNs can protect the host against bacterial, viral, fungal and parasitic infections. CpG-induced protection develops rapidly but persists for only a few weeks. Preclinical and clinical trials suggest that CpG ODNs can be used safely to activate the human immune system.

Coencapsulation of CpG Oligodeoxynucleotides with RecombinantLeishmania majorStress-Inducible Protein 1 in Liposome Enhances Immune Response and Protection against Leishmaniasis in Immunized BALB/c Mice

“…The smallest number of live parasites was seen for the group of mice immunized with Lip-rLmSTI1-CpG ODN, which paralleled the footpad swelling results. It seems that CpG ODN in free form induces protection for a shorter time and that liposomal CpG ODN induces protection for a longer time, as described by others (20). On the other hand, CpG ODN as an immunoadjuvant needs some delivery system to maintain and enhance the immunoadjuvant activity.…”

“…Synthetic oligodeoxynucleotides (ODN) expressing CpG motifs mimic the immunostimulatory activity of bacterial DNA and mediate a variety of immunological functions, including stimulation of a Th1 or Th2 immune response, based on their sequence; therefore, CpG ODN are able to act as immunoadjuvants to accelerate and boost antigen-specific immune responses 5-to 500-fold (21). The innate immune response elicited by CpG ODN peaks within days and is maintained for about 2 weeks (20). The immunoadjuvant effect of CpG ODN is optimized by maintaining close physical contact between the antigen and CpG ODN (21).…”

“…Considering the difficulty in the chemical conjugation procedure and the possibility of altering the threedimensional structure of an antigen, thereby changing its immunogenicity, it is of particular interest to explore other means of CpG ODN-antigen association (23). One strategy to extend the duration of CpG activity is the encapsulation of CpG ODN in liposomes (20). Liposomes have been used as a delivery vehicle to provide a close association of CpG ODN with antigen, and they enhanced the immune response (21).…”

CpG Oligodeoxynucleotides Protect Newborn Mice from a Lethal Challenge with the Neurotropic Tacaribe Arenavirus

“…Empirical data suggest that, in infections with rapidly dividing pathogens, optimal protection is evident when the CpG ODNs are administered 3-6 days before infection (29). In contrast, for infections that have slower kinetics such as leishmaniasis, CpG ODN can induce a protective response even when administered weeks after infection (30).…”

Prevention and Treatment of Cutaneous Leishmaniasis in Primates by Using Synthetic Type D/A Oligodeoxynucleotides Expressing CpG Motifs

“…Several studies of mice had shown that preactivation of the immune system with CpG ODN is required to achieve protection (15). To assess whether administration of CpG ODN prior to infection was necessary for protection, a group of four rhesus macaques were challenged with L. major and treated one time with D/A ODN i.d.…”