595. Nasal Delivery of Adenovirus Expressing the Ebola Glycoprotein Protects Mice Against Ebola Virus in the Presence of Preexisting Immunity to the Vaccine Carrier
Notice bibliographique
Résumé
The Ebola hemorrhagic fever virus has drawn increasing interest in the past years due to an augmentation in the number of natural outbreaks and its potential use as a bioterror agent. To date, only vaccine based on Vesicular Stomatitis virus and Adenovirus as the vaccine carrier have successfully protected nonhuman primates against a lethal dose of Ebola virus. Adenovirus vector derived from human adenovirus serotype 5 (AdHu5) has the advantage of having a well document track record following in vivo administration to thousand of individuals in different clinical trials. However, natural exposure to Adenovirus may result in the generation of a potent immunity capable of compromising adenovirus-based vaccine efficacy. 30 to 50% of the human population in North America has levels of serum antibodies that can neutralize relatively high doses of AdHu5. The present study evaluated mucosal vaccination of mice with AdHu5 expressing the Ebola glycoprotein (Ad-EboGP) and the impact of pre-existing immunity to the Adenovirus vector on vaccine efficacy. Intramuscular (I.M.), oral or nasal administration of Ad-EboGP fully protected mice against a lethal challenge with mouse-adapted Ebola virus. However, oral or I.M. vaccination of mice pretreated with pooled human antibodies, mimicking the presence of pre-existing immunity as evidenced by neutralizing antibody (NAB) to AdHu5 in mice sera, resulted in 0 to 10% survival after challenge with mouse-adapted Ebola virus. Interestingly, nasalvaccination with Ad-EboGP was protective even in the presence of preexisting immunity and resulted in 100% survival with no weight loss after challenge with Ebola virus. In untreated mice, T (INF-γ positive CD8 T cells following peptide re-stimulation) and B cell (NAB) responses were detected in all EboGP vaccinated groups although both responses were lower in mice receiving oral or nasal immunization when compared to mice administered I.M.. The presence of pre-existing immunity severely compromised the T and B cell responses in mice vaccinated orally or I.M. but not in mice receiving nasal immunization. Interestingly, PEGylation of the adenovirus vector partially rescued the B cell response but diminished the T cell response after oral vaccination of mice with pre-existing immunity and failed to improve survival. This study highlights the importance of vaccine delivery routes with regards to efficacy in the presence or absence of pre-existing immunity and provides new evidence for successful vaccination with AdHu5 and possibly readministration. James Wilson had equity in Targeted Genetics at the time of the study.
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Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,001 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».