Rèsumè
Objectifs
Les surfaces muqueuses de l’arbre respiratoire constituant une porte d’entrée très importante pour de nombreux agents pathogènes, bactériens ou viraux, elles apparaissent comme un site critique pour la réponse immune. Ainsi, des vaccins stimulant cette immunité locale sembleraient constituer une approche intéressante dans la prévention de ces infections. Après avoir détaillé les différents mécanismes mis en jeu dans cette immunité muqueuse, cette étude a pour but d’analyser le principe d’une telle vaccination et les différents vaccins administrables par voie respiratoire.
Immunité muqueuse
Les principaux anticorps sécrétés localement appartiennent à l’isotype IgA (S-IgA), les anticorps de type IgM (S-IgM) et IgG (S-IgG) ayant un rôle encore largement discuté. Les cellules effectrices qui dominent au niveau de la muqueuse ne sont pas des cellules IgA de type B, mais des lymphocytes T qui peuvent représenter jusqu’à 80 % de la totalité des populations lymphocytaires de la muqueuse.
Immunoprophylaxie par voie respiratoire
Des immunoglobulines spécifiques administrées localement peuvent prévenir des infections virales comme cela a été démontré pour le VRS ; mais les quantités d’anticorps nécessaires pour être actives sont très importantes et difficiles à obtenir.
Parmi les facteurs susceptibles d’induire une réponse immune muqueuse et une immunité à médiation cellulaire, on retrouve la voie orale ou respiratoire et des virus réplicatifs.
À ce jour, très peu de vaccins antiviraux muqueux ont vu le jour et le seul exemple pour les virus respiratoires reste le vaccin grippal atténué administré par voie nasale.
D’autres vaccins commercialisés par voie parentérale ont été utilisés expérimentalement par voie nasale. Qu’il s’agisse de vaccins vivants (varicelle, rougeole) ou inactivés (grippe injectable), ils n’induisent par cette voie inhabituelle qu’une réponse locale modérée.
Conclusion
Il apparaît donc dans l’état actuel de nos connaissances et des vaccins disponibles que la voie muqueuse ne constitue pas une voie essentielle et incontournable pour élaborer un vaccin actif contre des virus respiratoires.
Mais l’exemple du vaccin grippe atténué administré par voie nasale est à lui seul prometteur pour l’avenir de la vaccination par voie muqueuse et d’autres approches plus sophistiquées pourraient voir le jour dans les années à venir.
Mots-clés: Vaccination muqueuse, virus, muqueuse respiratoire, IgA sécrétoires, vaccins grippaux vivants atténués
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.
Key words: Mucosal vaccination, virus, respiratory tract, S-IgA, cold-adaptated influenza vaccines
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