Influenza preimmunity increases vaccination efficacy by influencing antibody longevity, neutralization activity, and epitope specificity
Notice bibliographique
Résumé
ABSTRACT Influenza virus infections are a recurrent public health problem causing millions of hospitalizations each year despite vaccination efforts. The well-known yearly cycling of influenza viruses is the result of the reciprocal and coevolutionary relationship between the host and virus. Together, from the frequent infections and yearly vaccinations humans build a complex immune history over their lifetimes. Despite the prominence of immune history, vaccines are rarely evaluated in the imprinted (preimmune) host. We developed a ferret model for this purpose where ferrets were imprinted with a sublethal dose of the historical seasonal H1N1 strain A/USSR/90/1977 (USSR/77). A +60 day recovery period was given to build immune memory prior to vaccination with a split virion QIV vaccine. To evaluate protection, the ferrets were challenged with a 2009 H1N1 pandemic virus matching the vaccine antigens. The preimmune-vaccinated ferrets did not experience significant disease during challenge while the naïve-vaccinated group were the most severe. Hemagglutination inhibition (HAI) assays showed that preimmune ferrets had a faster and longer antibody response post vaccination for all vaccine antigens compared to minimal HAI responses in the naïve-vaccinated group. To investigate the immune mechanisms leading to disease protection in the preimmune ferrets, we performed microneutralization and isotype ELISA assays. Microneutralization suggested preimmune ferrets developed antibodies that were more functional for virus neutralization. Antibody isotype profiling indicated that virus specific antibodies in the preimmune-vaccinated ferrets was dominated by the IgG isotype suggesting B cell maturity and possible plasticity in a pre-existing B cell. Surprisingly, the naïve-vaccinated ferrets developed a more severe disease with less virus neutralization suggesting improper immunological processing of vaccine antigens. Together, these results showed the preimmune host had greater responses to vaccination, and the predominant IgG virus specific antibodies suggested a flexible long-lived B cell response. These results are important and should be considered for vaccine design. AUTHOR SUMMARY The influenza virus is a significant threat to human health and the economy despite large-scale vaccination efforts. The low effectiveness of the seasonal influenza vaccine is attributed to the frequently mutating virus enabling people to have several influenza virus infections throughout their lifetimes. As people are susceptible to multiple infections, they build a complex immune history. Despite this, vaccines are often not evaluated in animals with an immune history. Here we developed a ferret model that had previously been infected with a historical influenza virus to evaluate vaccine responses to current vaccines. Ferrets were infected with a sublethal does of a historical virus, A/USSR/90/1977, to develop a preimmune background. Preimmune ferrets were vaccinated with the Sanofi quadrivalent influenza vaccine and the antibody responses were investigated after vaccination. Our results showed that preimmune ferrets had a stronger antibody response following vaccination and the antibodies developed were older and better at neutralizing influenza virus at a virus challenge. Clinically, preimmune-vaccinated ferrets developed a milder disease during challenge compared to naïve-vaccinated ferrets. This work indicates that the host responses to vaccination are dependent on the host background and that influenza vaccine development and evaluation should take host influenza background into account.
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Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 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 source (Gemma direct ou Codex distillé), 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 ».