Arthur M. Krieg

CpG ODN As a Th1 Immune Enhancer for Prophylactic and Therapeutic Vaccines

Adaptive immunity, which comes about through highly specific recognition of antigenic epitopes on B and T cells, results in the development of antigen-specific antibodies and cytotoxic T-cell responses. However, these processes rely very heavily on simultaneous activation of cells of the innate immune system including dendritic cells (DCs), macrophages, and monocytes. Cells of the innate immune system lack highly specific antigen receptors, but rather rely on a set of pattern recognition receptors (PRRs), which have a general ability to detect pathogen-associated molecular patterns (PAMPs) that are specific molecular structures found in pathogens, but not in self tissues (1,2). Many of the PRRs are found in the family of Toll-like receptors (TLR), of which at least 10 types have been identified. Examples of PAMPs that PRRs detect include endotoxins, flagellin, high mannose proteins, single- and double-stranded viral ribonucleic acids (RNAs) and the unmethylated CpG dinucleotides in particular base contexts (CpG motifs) that are prevalent in bacterial and many viral deoxyribonucleic acids (DNAs), but are heavily suppressed and methylated in vertebrate genomes (1, 2, 3, 4, 5). The immune system appears to use the presence of these PAMPs as a “danger signal” that indicates the presence of infection and activates appropriate defense pathways. Recently there has been broad interest in testing and developing such “danger signal” ligands of PRRs for immune stimulation, including use as adjuvants to enhance antigen-specific responses.