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Targeting Neutrophils to Improve Protection by Sublingual Vaccines

Rowe, JC;

Vaccines are biological preparations that are used to educate the immune system and make it develop a long lasting or adaptive immunity directed specifically against one or several components of the preparations. Vaccines containing parts or components of disease-causing microorganism have been used in medical science for over 300 years in a variety of capacities to help control the burden of infectious diseases in both humans and animals. Indeed, new frontiers continue to emerge regarding broader applications of vaccination, including novel approaches to treat cancer or ways to prevent future obesity. More specific to infectious diseases, most infectious agents enter the host via exposed mucosal surfaces and the development of novel vaccination approaches to successfully protect both the general bloodstream and mucosal tissues is vital to protecting public health in the modern era. In this thesis, a novel approach to improve the efficacy of mucosal vaccination is described using a sublingual vaccine model. Neutrophils are the main myeloid cell subset found in the body and are among the first cells recruited to sites of inflammation, or vaccination. This thesis describes how the supplementation of a sublingual vaccine with molecules that suppress neutrophil elastase improves the kinetic of subsequent antibody responses and leads to the production of broad antibody responses, including secretory IgA at mucosal tissue sites, and is accompanied by broad helper T cell induction.