Briefly, HSPs have been used in phase I and phase II clinical trials for a glioblastoma vaccine, a trial for a protective H9N2 influenza vaccine in chickens, and a phase II clinical trial for a type 1 diabetes therapy. While the notion of heat shock proteins as immunogens or adjuvants may seem counterintuitive, they have been demonstrated to be potent vaccine components. These proteins are part of the constitutive proteome, but their expression is increased when the need arises. Induced proteins may include chaperones that assist in the folding of newly synthesized proteins, prevent aggregation of proteins during heat shock, and repair proteins that have been damaged or misfolded by heat shock, all without being part of the final protein structure. Exposure to these new environments can mean the bacteria experience changes in temperature, nutrient availability, osmolarity, and pH, all of which trigger a stress response and influence expression of heat shock proteins (HSPs). In addition, we highlight literature showcasing the immunomodulation effects these proteins can have on the immune system, also making them potential adjuvants or immunotherapeutics.īacteria gain entry into a host through damage to the skin or contact with the mucosa whereupon they must invade or otherwise traverse the mucosal barrier to invade the host. Herein we highlight literature showing that intracellular chaperone proteins GroEL and DnaK, which were originally identified as playing a role in protein folding, are relocated to the cell surface or are secreted during invasion and therefore may be recognized by the host immune system as antigens. Stress response proteins such as heat shock proteins and chaperones are some of the proteins that undergo changes in levels of expression and/or changes in cellular localization from the cytosol to the cell surface or the secretome, making them potential immunogens for vaccine development. Even when an organism has already penetrated the blood or lymphatics and it then enters another organ or a cell, it can respond to these new conditions by increasing the expression of virulence factors to aid in bacterial adherence, invasion, or immune evasion. Immediately upon entry into the host organism, bacteria are exposed to a different environment, which includes changes in temperature, osmotic pressure, pH, etc. These differentially expressed proteins may be suitable to use for vaccine antigens if they are virulence factors. Bacteria do not simply express a constitutive panel of proteins but they instead undergo dynamic changes in their protein repertoire in response to changes in nutritional status and when exposed to different environments.
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