β‐Glucan particles as a vaccine platform with intrinsic adjuvanticity (469.3)

Abstract

Most licensed vaccines work by promoting protective antibody responses. However, some populations, such as the elderly and the immunocompromised, generally have poor antibody responses to conventional vaccines. Moreover, for many infectious and neoplastic diseases, vaccines that arm adaptive T cell responses appear necessary. Thus, a major challenge in vaccinology is the development of platforms and adjuvants that effectively promote protective T cell and antibody responses. The immune system has evolved to innately recognize components of the fungal cell wall, particularly β‐glucans. Our research has focused on how innate recognition of the fungal cell wall can be exploited for vaccine development. To achieve this aim, we have used glucan particles (GPs) as a novel vaccine platform. GPs are hollow, highly purified microcapsules prepared from Saccharomyces cerevisiae cell walls. GPs are composed predominantly of β‐1,3‐glucan and are recognized by β‐glucan receptors (particularly Dectin‐1) on dendritic cells and other phagocytes. GPs also potently activate complement, resulting in opsonization and recognition by complement receptors. GPs can be loaded with antigens and immunomodulators such that the “payload” is released following phagocytosis. We have demonstrated robust and long‐lasting antigen‐specific T cell (Th1‐ and Th17‐biased) and antibody responses following immunization of mice with GPs “encapsulated” with antibody. Moreover, vaccination of mice with GPs loaded with fungal antigens can protect mice against lethal challenges with the pathogenic fungi Cryptococcus neoformans and Histoplasma capsulatum.