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Vaccines for the 21st Century: A Tool for Decisionmaking
and proteins currently licensed for use in the United States, only 4 (OPV, rotavirus, adenovirus, and typhoid) are administered orally (CDC, 1994b) and none are given intranasally. Although parenterally administered vaccines induce protective immune responses, they rarely, if ever, induce mucosal immune responses that may prevent infection at the site of initial contact between the host and the infectious agent. The following sections describe some of the cellular and molecular components of the mucosal immune system of relevance to current mucosal vaccine strategies.
Mucosal Immune System Organization
Generally, foreign antigens and pathogens are encountered through ingestion or by inhalation, and the host has evolved in these regions organized lymphoid tissues that facilitate their uptake. These inductive sites contain B and T lymphocytes that in the presence of appropriate antigen-presenting cells, respond to the encountered antigen by developing into effector and memory B and T cells. These antigen-specific B- and T-cell populations then emigrate from the inductive environment via lymphatic drainage, circulate through the bloodstream, and home to mucosal effector regions using distinct homing receptors that recognize mucosal addressins. Thus, mucosal effector sites include these more diffuse tissues where antigen-specific T and B lymphocytes ultimately reside and perform their respective functions (i.e., cytokine and antibody synthesis, respectively) to protect mucosal surfaces.
After the initial exposure to antigen in mucosal inductive sites, mucosal lymphocytes leave the inductive sites and home to mucosal effector tissues. Antigen-specific mucosal effector cells include IgA-producing plasma cells as well as B and T lymphocytes. Polymeric, usually dimeric, IgA is the primary immunoglobulin involved in the protection of mucosal surfaces and is locally produced in the gastrointestinal and upper respiratory tracts, nose, middle ear, gall bladder, uterine mucosa, and biliary tree as well as glandular tissues such as salivary, lactating mammary, prostate, and lacrimal glands (Phillips-Quagliata et al., 1994). The observation that antigen-specific S-IgA responses may be detected at mucosal surfaces other than the inductive site where antigen uptake initially occurred led to the discovery of the common mucosal immune system. Studies to elucidate the common mucosal immune system pathway showed that immunization of one mucosal inductive site could induce mucosal immune responses in all mucosal effector tissues. The common mucosal immune system provides a unique opportunity to develop mucosal vaccines that can be delivered orally or intranasally but that subsequently result in mucosal immunity at sites where immune protection is most desirable.
One major hallmark of the mucosal immune response is the presence of IgA antibodies at mucosal surfaces. The importance of IgA transport across epithelial surfaces to external secretions should be considered when vaccines are being designed to prevent infections that occur at mucosal surfaces. Passive transfer