Covid : qu’est-ce que l’ARN messager et comment est-il utilisé pour les vaccins ?

Dr Edinam Agbenu
Légende image,Dr Edinam Agbenu

Dr Edinam Agbenu, la responsable de la sécurité et de la qualité des vaccins au sein du Bureau régional de l’Organisation mondiale de la Santé pour l’Afrique, explique à la BBC ce qu’est l’ARN messager (acide ribonucléique messager) et son utilisation dans les vaccins, notamment ceux contre le Covid-19.

La spécialiste togolaise s’est entretenue avec Benoît Alméras de l’émission Question Santé.

Qu’est-ce que l’ARN messager en termes simples ?

Les organismes vivants sont faits de cellules et de molécules. Et donc, parmi les molécules dont nous sommes constitués, il y a ce qu’on appelle l’ARN messager. Nous connaissons tous les protéines, par exemple c’est le constituant majeur des viandes. Pour fabriquer les protéines, il faut que l’information soit lue à partir du noyau des cellules. Dans le noyau, nous avons les chromosomes, l’ADN. Et pour que le noyau s’exprime en protéines, il y a une étape intermédiaire qu’on appelle ARN messager et qui, en fait est comme une photocopie. Vous avez un livre, vous voulez le scanner, vous scannez une page dont vous avez besoin. Cette page que vous avez scannée et que vous pouvez envoyer plus loin, elle s’appelle ARN messager.

Alors, de quand date la première utilisation de l’ARN messager pour un usage vaccinal ?

Le vaccin ARN messager de Pfeizer
Légende image,Le vaccin ARN messager de Pfeizer

Les ARN messagers sont en étude depuis les années 90. L’intention première était justement d’améliorer l’arsenal thérapeutique dont les vaccins. Et ça a commencé dans les années 90. Par la suite, au fil des ans, il a été question d’améliorer la stabilité de cet ARN messager parce que vous savez, lorsqu’on administre une substance à un organisme vivant, la substance va être prise en charge et détruite rapidement. Mais pour que l’ARNm puisse effectivement mettre en œuvre la réponse immunitaire, donc la vaccination, il faut qu’il passe un peu plus de temps, au moins qu’il arrive dans le cytoplasme des cellules ; s’il est détruit trop rapidement, ce n’est pas bon. Donc, il fallu trouver les moyens de stabiliser un peu tout ça. Cela a pris un peu de temps, mais avec la pandémie Covid, cette étude qui était destinée à servir à des vaccins contre le cancer etc, les chercheurs se sont mis ensemble et ont rapidement fait avancer la production des vaccins à ARN messager.

En quoi la pandémie de Covid a facilité le développement de cette technologie ?

Bon, parce que la pandémie à Covid-19 nous a tous un peu pris de court et il fallait trouver une réponse rapide. La technologie qui permettait de produire une quantité suffisante de vaccins pour arrêter le désastre était quand même que cette technologie ARN messager marche. Et il était question d’abord d’isoler, quel antigène peut être utilisé. L’antigène, c’est ce à quoi notre organisme va reconnaitre le virus comme un agresseur pour pouvoir développer la réponse de défense, la réponse immunitaire. Et le virus est fait de plusieurs antigènes. Il faut trouver le bon antigène que l’on va utiliser pour entrainer l’organisme à se défendre contre le virus. Cela ne dépend pas de l’ARN messager. Mais une fois que ça a été sélectionné, comment fabriquer le vaccin qui répond à cet antigène en très grande quantité dans un temps record. Le partage d’informations et l’existence d’une étude déjà avancée sur les ARN messagers a permis juste de saisir cette opportunité.

Les vaccins ARN messagers des sociétés PfeizerBioNtech et Moderna sont réputés plus efficaces contre le coronavirus, mais concrètement, quels sont les avantages de ces ARN messagers comparés à d’autres vaccins qui sont basés sur d’autres technologies plus anciennes ?

Par rapport aux vaccins traditionnels, je l’appellerais un transfert de technologie du laboratoire à l’organisme. Traditionnellement, vous avez un virus. On peut prendre le virus vivant et l’injecter. L’organisme va se défendre contre ce virus qui est affaibli. On appelle ça, virus atténué. Mais le risque avec un virus atténué est qu’il y ait une réversion et un retour à la forme virulente. L’atténuation, quand même, a permis d’obtenir des vaccins contre la fièvre jaune, contre la rougeole, etc. On a une autre technologie qui permet d’inactiver, donc de tuer le virus et de l’envoyer. La grande limite d’un virus qui est tué, c’est qu’il ne circule pas beaucoup dans l’organisme. Donc, il passe très vite, un peu trop vite et on n’a pas une réponse qui dure dans le temps.

Chaine de production du vaccin ARNm dans un laboratoire de Pfeizer à Marbourg en Allemagne
Légende image,Chaine de production du vaccin ARNm dans un laboratoire de Pfeizer à Marbourg en Allemagne

Dans le cadre de la technologie qui utilise l’ARN messager, on fait un transfert de technologie. Donc, une fois qu’on a retrouvé la protéine du virus qui va donner une bonne réponse, cet ARN messager peut maintenant produire cette protéine depuis l’intérieur de l’organisme en quantités suffisantes pour générer la réponse immunitaire. Il faut savoir que si on le fait, c’est un peu comme si autrefois en Afrique on achetait des motos déjà faites en Chine, aujourd’hui, on fait venir les pièces détachées et on les fabrique ici. Et on sait qu’il y a déjà certaines industries qui ont juste le modèle et qui reproduisent. Donc, en fait c’est juste un transfert de technologie, de l’industrie à l’organisme, l’ARN messager ; ça permet de diminuer la quantité qu’on administre à la personne ; ça permet d’obtenir une stimulation du système immunitaire plus longtemps. Et il faut savoir qu’il y a une amplification de la quantité de protéines qui est finalement présentée à l’organisme. Et ça permet aussi pour l’approvisionnement en vaccins de réduire le temps de production pour pouvoir suppléer aux besoins de la planète.

On a l’impression, à vous entendre, qu’il s’agit quasiment de vaccins miracles, en fait, qui sont plus rapides, qui sont potentiellement aussi plus efficaces, mais y-a-t-il des désavantages, des risques, voire des dangers à utiliser des vaccins à ARN messager ?

Tout produit étranger, tout corps étranger qu’on administre à un organisme est reconnu comme agresseur et l’organisme va lutter contre cela et cela va se manifester cliniquement par des signes que l’on aura. On aura la fièvre, on aura des maux de tête, etc. Certains d’entre eux étant graves. Et sur les données actuelles, les vaccins à ARN messagers utilisés jusqu’à présent se sont suivis de dix, voire cent fois moins d’effets indésirables que les autres vaccins.

Processus de fabrication de l'ARNm par le laboratoire BioNtech à Marbourg en Allemagne
Légende image,Processus de fabrication de l’ARNm par le laboratoire BioNtech à Marbourg en Allemagne

Alors, la grande question que les gens se posent par rapport aux vaccins ARN messagers, c’est que ce vaccin modifie le matériel génétique de l’individu. Il faut savoir que ce n’est pas envisageable. Et pourquoi est-ce qu’il n’est pas envisageable que l’ARN messager s’intègre dans le chromosome, c’est que le chromosome se trouve dans le noyau. L’ARN messager, il a une voie unidirectionnelle, il réside dans le cytoplasme. C’est un peu comme dans une maison, vous avez la membrane de la cellule, on peut considérer que c’est la clôture. Vous avez la cour, vous considérez que c’est le cytoplasme et vous avez le noyau, c’est un peu l’espace vital à l’intérieur. Donc, l’ARN messager reste dans le cytoplasme alors que le chromosome qui est en fait l’identité de l’individu se trouve dans le noyau.

Les vaccins ARN messager ont commencé à être développés bien avant la pandémie de Covid, mais je voudrais vous proposer un exercice de prospective. Quels sont les futurs développements pour ces vaccins ARN messager ?

La recherche sur les ARN messagers continue et un des grands objectifs, c’est d’améliorer la stabilité de cet ARN messager une fois qu’il est administré parce qu’il faudrait bien qu’il produise la protéine pour que cela donne la réponse immunitaire. Et un autre développement, c’est que tous les vaccins pour lesquels la production est un peu difficile, en termes de délai de production et autres, la recherche va continuer pour voir dans quelles mesures les vaccins ARN messagers pourraient être produits pour ça et un grand intérêt existe déjà pour les vaccins contre les cancers et certaines autres maladies évitables par la vaccination.

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