The development and widespread use of vaccines against infectious agents have been a great triumph of medical science. One reason for the success of currently available vaccines is that they are capable of inducing long-lived antibody responses, which are the principal agents of immune protection against most viruses and bacteria. Despite these successes, vaccination against intracellular organisms that require cell-mediated immunity, such as the agents of tuberculosis, malaria, leishmaniasis, and human immunodeficiency virus infection, are either not available or not uniformly effective. Owing to the substantial morbidity and mortality associated with these diseases worldwide, an understanding of the mechanisms involved in generating long-lived cellular immune responses has tremendous practical importance. For these reasons, a new form of vaccination, using DNA that contains the gene for the antigen of interest, is under intensive investigation, because it can engender both humoral and cellular immune re...

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DNA vaccines: immunology, application, and optimization*.

http://www.nanomedicinelab.com/wp-content/uploads/2012/03/12thslide05.pdf

Biomedical applications of functionalised carbon nanotubes

T helper type 1 (Th1) lymphocytes secrete secrete interleukin (IL)-2, interferon-gamma, and lymphotoxin-alpha and stimulate type 1 immunity, which is characterized by intense phagocytic activity. Conversely, Th2 cells secrete IL-4, IL-5, IL-9, IL-10, and IL-13 and stimulate type 2 immunity, which is characterized by high antibody titers. Type 1 and type 2 immunity are not strictly synonymous with cell-mediated and humoral immunity, because Th1 cells also stimulate moderate levels of antibody production, whereas Th2 cells actively suppress phagocytosis. For most infections, save those caused by large eukaryotic pathogens, type 1 immunity is protective, whereas type 2 responses assist with the resolution of cell-mediated inflammation. Severe systemic stress, immunosuppression, or overwhelming microbial inoculation causes the immune system to mount a type 2 response to an infection normally controlled by type 1 immunity. In such cases, administration of antimicrobial chemotherapy and exogenous cytokines restores systemic balance, which allows successful immune responses to clear the infection.

Type 1/Type 2 Immunity in Infectious Diseases

Nucleic acids containing unmethylated CpG dinucleotides and therapeutic utilities based on their ability to stimulate an immune response and to redirect a Th2 response to a Th1 response in a subject are disclosed. Methods for treating atopic diseases, including atopic dermatitis, are disclosed.

https://ir.uiowa.edu/cgi/viewcontent.cgi?article=1562&context=patents

Immunostimulatory nucleic acid molecules

Cross-presentation involves the uptake and processing of exogenous antigens within the major histocompatibility complex (MHC) class I pathway. This process is primarily performed by dendritic cells (DCs), which are not a single cell type but may be divided into several distinct subsets. Those expressing CD8alpha together with CD205, found primarily in the T-cell areas of the spleen and lymph nodes, are the major subset responsible for cross-presenting cellular antigens. This ability is likely to be important for the generation of cytotoxic T-cell immunity to a variety of antigens, particularly those associated with viral infection, tumorigenesis, and DNA vaccination. At present, it is unclear whether the CD8alpha-expressing DC subset captures antigen directly from target cells or obtains it indirectly from intermediary DCs that traffic from peripheral sites. In this review, we examine the molecular basis for cross-presentation, discuss the role of DC subsets, and examine the contribution of this process to immunity, with some emphasis on DNA vaccination.

Cross-presentation, dendritic cell subsets, and the generation of immunity to cellular antigens

We previously showed that bacterial DNA contains immunostimulatory motifs consisting of unmethylated CpG dinucleotides flanked by two 5' purines and two 3' pyrimidines. These motifs rapidly trigger an innate immune response, characterized by the production of IL-6, IL-12, and IFN-gamma. Since DNA vaccines are constructed from plasmids of bacterial DNA, we examined whether CpG motifs present in these plasmids contributed to the immunogenicity of DNA vaccines. In vitro experiments showed that DNA plasmids induced production of the same cytokines stimulated by bacterial DNA, an effect eliminated by DNase treatment. In vivo experiments showed that the immunogenicity of a DNA vaccine was significantly reduced by methylating its CpG motifs and was significantly increased by coadministering exogenous CpG-containing DNA. These findings support the conclusion that CpG motifs in the plasmid backbone of DNA vaccines play an important role in the induction of Ag-specific immunity.

Y Ishigatsubo

Papers

Contribution of CpG motifs to the immunogenicity of DNA vaccines.