Optimal induction of upper respiratory tract immunity to reovirus 1/L by combined upper and lower respiratory tract inoculation

Abstract

There has been an increasing interest in developing vaccines which are both easy to administer and which elicit functionally protective immune responses at mucosal and/or systemic sites. Intranasally administered vaccines meet the criteria of ease of administration and are thought to stimulate respiratory-mucosal immunity via interaction with nasal associated lymphoid tissues (NALT). The aim of this study was to gain a better understanding of how best to stimulate respiratory-mucosal immunity using a murine model of respiratory reovirus infection. Either a predominantly upper respiratory tract infection or a combination upper and lower respiratory tract infection was established by administering the same virus dose in either a small or large inoculum volume. These studies demonstrate that stimulation of NALT alone by an upper respiratory tract infection does not induce an optimal primary antibody response even in the nasal cavity. Effective immunity of both the upper and lower respiratory tract was obtained when a combination upper and lower respiratory tract infection was established. These results have important clinical implications since they suggest that effective respiratory mucosal immunity will be best achieved by the combined stimulation of both the upper and lower respiratory tract and will likely require both intranasal as well as inhaled aerosol delivery of antigen to the lower respiratory tract in humans.