The “Favor” of Chronic Infection and the “Gift” of Premunition Immunity

Abstract

Vaccine development that recapitulates premunition immunity has been unsuccessful because of an incomplete understanding of the immune response that is responsible for premunition. Current consensus in Leishmania major infection research has narrowed premunition immunity to a small population of terminally differentiate, non-replicating CD4+ effector T cells that are rapidly recruited to sites of re-infection and produce high amounts of interferon-gamma (IFN-γ). Premunition immunity associated with parasites such as L. major and Toxoplasma gondii, are a model for diseases caused by other persistent pathogens such as Salmonella enterica and Mycobacterium tuberculosis. These effector T cells require constant stimulation to a pathogen reservoir that repopulates itself indefinitely. The inability of delivering a platform capable of providing a depot of long lasting, intact antigen that induces this desired effect must be addressed if a vaccine is to ever convey premunition. Developing a vaccine that can initiate and maintain this chronic subclinical infection could be applied to many persistent infections where current vaccine technology is ineffective. New breakthroughs in polyanhydride nanoparticles (PAN) antigen preparation along with design of extended antigen delivery devices, such the vaccine platform extended antigen release (VPEAR) have now shown experimentally that antigen can be protected from degradation, delivered over an extended period of time, and maintain a population antigen-specific Th1 cells that produce IFN-γ.