The relative magnitude of transgene-specific adaptive immune responses induced by human and chimpanzee adenovirus vectors differs between laboratory animals and a target species
Adenovirus vaccine vectors generated from new viral serotypes are routinely screened in pre-clinical laboratory animal models to identify the most immunogenic and efficacious candidates for further evaluation in clinical human and veterinary settings. Here, we show that studies in a laboratory species do not necessarily predict the hierarchy of vector performance in other mammals. In mice, after intramuscular immunization, HAdV-5 (Human adenovirus C) based vectors elicited cellular and humoral adaptive responses of higher magnitudes compared to the chimpanzee adenovirus vectors ChAdOx1 and AdC68 from species Human adenovirus E. After HAdV-5 vaccination, transgene specific IFN-γ(+) CD8(+) T cell responses reached peak magnitude later than after ChAdOx1 and AdC68 vaccination, and exhibited a slower contraction to a memory phenotype. In cattle, cellular and humoral immune responses were at least equivalent, if not higher, in magnitude after ChAdOx1 vaccination compared to HAdV-5. Though we have not tested protective efficacy in a disease model, these findings have important implications for the selection of candidate vectors for further evaluation. We propose that vaccines based on ChAdOx1 or other Human adenovirus E serotypes could be at least as immunogenic as current licensed bovine vaccines based on HAdV-5..
Medienart: |
Artikel |
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Erscheinungsjahr: |
2015 |
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Erschienen: |
2015 |
Enthalten in: |
Zur Gesamtaufnahme - volume:33 |
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Enthalten in: |
Vaccine - 33(2015), 9, Seite 1121-1128 |
Sprache: |
Englisch |
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Beteiligte Personen: |
Dicks, Matthew D J [VerfasserIn] |
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Links: |
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doi: |
10.1016/j.vaccine.2015.01.042 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
OLC1956705341 |
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520 | |a Adenovirus vaccine vectors generated from new viral serotypes are routinely screened in pre-clinical laboratory animal models to identify the most immunogenic and efficacious candidates for further evaluation in clinical human and veterinary settings. Here, we show that studies in a laboratory species do not necessarily predict the hierarchy of vector performance in other mammals. In mice, after intramuscular immunization, HAdV-5 (Human adenovirus C) based vectors elicited cellular and humoral adaptive responses of higher magnitudes compared to the chimpanzee adenovirus vectors ChAdOx1 and AdC68 from species Human adenovirus E. After HAdV-5 vaccination, transgene specific IFN-γ(+) CD8(+) T cell responses reached peak magnitude later than after ChAdOx1 and AdC68 vaccination, and exhibited a slower contraction to a memory phenotype. In cattle, cellular and humoral immune responses were at least equivalent, if not higher, in magnitude after ChAdOx1 vaccination compared to HAdV-5. Though we have not tested protective efficacy in a disease model, these findings have important implications for the selection of candidate vectors for further evaluation. We propose that vaccines based on ChAdOx1 or other Human adenovirus E serotypes could be at least as immunogenic as current licensed bovine vaccines based on HAdV-5. | ||
540 | |a Nutzungsrecht: Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved. | ||
650 | 4 | |a Recombinant Proteins - genetics | |
650 | 4 | |a Vaccines, Synthetic - immunology | |
650 | 4 | |a Viral Vaccines - administration & dosage | |
650 | 4 | |a Adenoviridae - genetics | |
650 | 4 | |a CD8-Positive T-Lymphocytes - immunology | |
650 | 4 | |a Vaccines, Synthetic - administration & dosage | |
650 | 4 | |a Viral Vaccines - genetics | |
650 | 4 | |a Recombinant Proteins - immunology | |
650 | 4 | |a Interferon-gamma - secretion | |
650 | 4 | |a Viral Vaccines - immunology | |
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650 | 4 | |a Influenza | |
650 | 4 | |a Flow cytometry | |
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