F Denis1, S Hantz1, S Alain1. 1. EA 3175 « Biologie Moléculaire et Cellulaire des Micro-organismes », Laboratoire de Bactériologie-Virologie-Hygiène, CHU Dupuytren, 2, avenue Martin Luther King, 87042 Limoges.
Abstract
OBJECTIVE: As the mucosal surfaces of the respiratory tract represent a major portal of entry for most human viruses and many bacteria, they seem to be a critical component of the mammalian immunologic repertoire. Thus, vaccines stimulating this local immunity could represent an interesting approach to prevent these infections. After detailing the different mechanisms implied in this mucosal immunity, the aim of this study is to analyze the basis of such a vaccination and the different vaccines available to mucosal respiratory tract use. MUCOSAL IMMUNITY: The major antibody isotype in external secretions is secretory immunoglobin A (S-IgA); the role of IgM (S-IgM) and IgG (S-IgG) are actually questionned. It is, however, interesting that the major effector cells in the mucosal surfaces are not IgA B cells, but T lymphocytes that may represent up to 80% of the entire mucosal lymphoid cell population. IMMUNOPROPHYLAXIS BY THE MUCOSAL ROUTE: Passive antibodies were shown to protect against mucosal viral infections, such as those caused by RSV, but very high quantities of passive antibodies are needed to restrict virus replication on mucosal surface.In general, factors which favor development of mucosal antibody and cell mediated immune responses include the oral or respiratory immunization and the replicating nature of the vaccine agents. However, to date only a few vaccines have become available to mucosal respiratory tract use, and cold-adapted influenza virus vaccines is the only one available using nasal route. Other parenteral licensed vaccines have not been recommended for mucosal administration. Some of them have been experimentally used with nasal administration of replicating agents (varicella and measles vaccines) or non replicating agents (influenza inactivated vaccine), but have been found to induce a very low mucosal response. CONCLUSION: Based on the experience with existing vaccines, the development of mucosal immunity or administration of vaccines via the mucosal route is clearly not a prerequisite today for control or prevention of most viral infectious respiratory diseases or diseases with respiratory tract as a route of contamination. But the example of live attenuated intranasal influenza vaccine inducing both systemic and local immune response without immunopathology, is promising for the future of the mucosal immunization against respiratory viral infections.
OBJECTIVE: As the mucosal surfaces of the respiratory tract represent a major portal of entry for most human viruses and many bacteria, they seem to be a critical component of the mammalian immunologic repertoire. Thus, vaccines stimulating this local immunity could represent an interesting approach to prevent these infections. After detailing the different mechanisms implied in this mucosal immunity, the aim of this study is to analyze the basis of such a vaccination and the different vaccines available to mucosal respiratory tract use. MUCOSAL IMMUNITY: The major antibody isotype in external secretions is secretory immunoglobin A (S-IgA); the role of IgM (S-IgM) and IgG (S-IgG) are actually questionned. It is, however, interesting that the major effector cells in the mucosal surfaces are not IgA B cells, but T lymphocytes that may represent up to 80% of the entire mucosal lymphoid cell population. IMMUNOPROPHYLAXIS BY THE MUCOSAL ROUTE: Passive antibodies were shown to protect against mucosal viral infections, such as those caused by RSV, but very high quantities of passive antibodies are needed to restrict virus replication on mucosal surface.In general, factors which favor development of mucosal antibody and cell mediated immune responses include the oral or respiratory immunization and the replicating nature of the vaccine agents. However, to date only a few vaccines have become available to mucosal respiratory tract use, and cold-adapted influenza virus vaccines is the only one available using nasal route. Other parenteral licensed vaccines have not been recommended for mucosal administration. Some of them have been experimentally used with nasal administration of replicating agents (varicella and measles vaccines) or non replicating agents (influenza inactivated vaccine), but have been found to induce a very low mucosal response. CONCLUSION: Based on the experience with existing vaccines, the development of mucosal immunity or administration of vaccines via the mucosal route is clearly not a prerequisite today for control or prevention of most viral infectious respiratory diseases or diseases with respiratory tract as a route of contamination. But the example of live attenuated intranasal influenza vaccine inducing both systemic and local immune response without immunopathology, is promising for the future of the mucosal immunization against respiratory viral infections.