Department of Microbiology & Immunology Seminar: “CpG and Therapeutic Vaccines”

Title: “CpG and Therapeutic Vaccines”

Speaker:
Joseph A. Bellanti, MD
Professor of Pediatrics and Microbiology-Immunology (Emeritus), Director, International Center for Interdisciplinary Studies of Immunology (ICISI), GUMC, Washington, DC

Abstract:
Preventive vaccines, traditionally associated with infectious diseases, such as measles, mumps and rubella, are administered to individuals who are at risk of contracting a specific infectious disease but have not yet been exposed to the pathogen. Their primary aim is to establish protective immunity and thwart future infections. Therapeutic vaccines, a more recent concept in vaccine usage, extends beyond infectious diseases to encompass the treatment of various medical conditions, including allergic diseases, autoimmune disorders, chronic infectious diseases, hypersensitivity diseases, and cancers driven by disordered or dysfunctional immune system responses. CpG oligodeoxynucleotides (CpG ODNs) have provided a newer basis for preventive vaccines as Th1-type immune stimulants that, by stimulating the TLR9 receptor, have proven to be a highly effective adjuvants for vaccines directed against infectious diseases. A crucial aspect of the role of CpG motifs in immunology, which forms the central focus of this presentation, lies in the recent discovery that when CpG motifs remain unmethylated, they act as immunostimulants, actively enhancing the immune response. Conversely, when these CpG motifs undergo methylation, they transition into immune silencing agonists. Recent research findings from our laboratory have shown that this silencing effect of methylated DNA is achieved through the induction of regulatory T cells (Treg cells) by methylated motifs. Since most of the CpG motifs in bacteria of the GI microbiome are unmethylated and therefore capable of inducing Th1 adjuvant-induced inflammatory responses while the CpG from commensal bacteria, such as Bifidobacterium longum subsp. infantis shown by our studies are methylated, we hypothesized that the methylated CpG repeats could be the responsible moieties for Treg induction. The results of both our in vitro and ongoing murine in vivo studies support this hypothesis.