Mucosal vaccination has many attractive features, including easy and painless administration, potential for mass immunization in case of emergencies, and reduced cost of production, storage, and delivery. Only the mucosal vaccines consistently promote immune responses at the most common sites of entry of infectious agents. The coronavirus responsible for severe acute respiratory syndrome (SARS) infects the host via mucosal tissues of the respiratory tract, where both mucosal antibodies and cell-mediated immune (CMI) responses could provide the host with lifesaving protection. The sequence of systemic priming followed by mucosal boosting provides vigorous humoral and cellular immune responses in both the mucosal and systemic compartments-with minimal danger of inducing tolerance in the cell-mediated arm of the immune response. The mucosal antibodies (Abs)-predominantly IgA and to a lesser degree IgG-exhibit their protective function by mechanisms that are distinct from specific antibodies present in the plasma. Inhibition of microbial adherence is a critical initial step for the protection of the host and can be mediated by both the specific and nonspecific mechanisms. © 2005 Elsevier Inc. All rights reserved.