Immune Responses to Microbes

34 IMMUNE RESPONSES TO MICROBES Two important vaccine advances have been the development of nanoparticle-based vaccine formulations and the identification of unique microbial products that are agonists for immunologic receptors: virus-like particles (VLPs) or nanoparticles, and Toll-Like Receptor (TLR) agonists, respectively.1-3 The immune system continuously screens for and interacts with microbes, identifying them as foreign and targeting them for immune responses. The immune system has evolved to use these unique physical and chemical attributes, TLRs for instance, to recognize microbes and specifically respond with protective responses. Bacteria and viruses, in essence, are naturally occurring micro/nanoparticulates that produce and are decorated with TLR agonists and assorted molecules, some of which are protective antigens. When antigen-presenting cells (APCs) of the innate immune system interact with the microbes’ particle/TLR agonist structures, the APCs are stimulated to internalize the particles into endocytic vesicles and process them for immune presentation. APCs far more efficiently recognize and internalize these particles compared soluble molecules. The presentation of internalized antigens by APC involves processing the protein antigens into peptide fragments that bind to Major Histocompatibility Complex (MHC) proteins expressed on their surfaces. APCs interacting with microbes are also directly stimulated by the microbes’ TLR agonists and respond by producing immunestimulatory signals, like co-stimulatory cell surface molecules and secreted cytokines that stimulate surrounding T and B lymphocytes. Antigen-specific T lymphocytes recognize the presented antigen fragments on APC via their T cell receptors and are stimulated by APCs’ co-stimulatory signals and cytokines. These stimulated T lymphocytes then proliferate, expanding Vaccine Technologies & the Rationale for New Nanoparticle Formulations By: Robert S. Becker, PhD, MBA, and Mark A. Mitchnick, MD