Rapid Induction of Protective Immunity Against Biothreat Agents Using CPG-Based Oligonucleotides

摘要

This research project examines the ability of synthetic oligonucleotides (ODN) containing immunostimulatory 'CpG motifs' to trigger the innate immune system, thereby improving the host's ability to survive infection by biowarfare agents. Additional studies examining the ability of these CpG ODN to act as adjuvants when co-administered with vaccines being developed to prevent infection by biowarfare pathogens are also being pursued. Our initial results showed that CpG ODN protected mice against a variety of bacterial and viral pathogens, including Anthrax, Ebola, Listeria, and Tularemia. When used as vaccine adjuvants, these CpG ODN significantly boost antigen-specific IgC and type 1 cytokine production in both muring and non-human primate models. Recent studies focused on (1) identifying the optimal type and number of BpG motifs needed to stimulate human immune cells, (2) establishing that these CpC ODN could protect against pathogen challenge in non-human primates and (3)that these CpG ODN could promote the induction of antigen-specific immune responses in non- human primates. Results indicate that CpG ODN need to contain multiple different CpG motifs to stimulate PBMC form diverse human donors. These ODN were found to protect rhesus macaques against pathogen challenge, and to augment the immunogenicity of co-administered vaccines (including AVA, rPA, and HKLV) in macaques. Serum transfer studies indicate that CpG ODN increase the magnitude and rapidity of the protective immune response elicited by vaccines against anthrax.