Vaccine vectors derived from a large collection of simian adenoviruses induce potent cellular immunity across multiple species
| Autor: | Kira Smith, Agostino Cirillo, Katie J. Ewer, Carly M. Bliss, M. Bartiromo, Virginia Ammendola, Riccardo Cortese, Angela Sparacino, Cinzia Traboni, Eleanor Barnes, M. Naddeo, Adrian V. S. Hill, Ayako Kurioka, Maria Raffaella Ambrosio, Stefano Colloca, Alfredo Nicosia, Annalisa Meola, Loredana Siani, Fabiana Grazioli, Paul Klenerman, Geraldine O'Hara, Nicholas A. Anagnostou, Maria Luisa Esposito, Stefania Capone, Antonella Folgori |
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| Přispěvatelé: | S., Colloca, E., Barne, A., Folgori, V., Ammendola, S., Capone, A., Cirillo, L., Siani, M., Naddeo, F., Grazioli, M. L., Esposito, M., Ambrosio, A., Sparacino, M., Bartiromo, A., Meola, K., Smith, A., Kurioka, G. A., O'Hara, K. J., Ewer, N., Anagnostou, C., Bli, A. V. S., Hill, C., Traboni, P., Klenerman, R., Cortese, Nicosia, Alfredo |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Serotype
Cellular immunity Pan troglodytes T cell Genetic Vectors Enzyme-Linked Immunosorbent Assay CD8-Positive T-Lymphocytes IMMUNOGENICITY medicine.disease_cause DENDRITIC CELLS ANTI-AD5 IMMUNITY Article Adenoviridae Cell Line Interferon-gamma Mice Immune system Species Specificity Immunity parasitic diseases medicine Animals Humans Potency Phylogeny Immunity Cellular PLASMODIUM-FALCIPARUM Dose-Response Relationship Drug biology NONHUMAN-PRIMATES General Medicine HIV-1 VACCINE Virology medicine.anatomical_structure Immune System viru Immunology PRIME-BOOST REGIMENS biology.protein Adenoviruses Simian Antibody RHESUS-MONKEYS HEALTHY-ADULTS |
| DOI: | 10.1126/scitranslmed.3002925 |
| Popis: | Replication defective Adenovirus vectors based on the human serotype 5 (Ad5) have been shown to induce protective immune responses against diverse pathogens and cancer in animal models and to elicit robust and sustained cellular immunity in humans. However, most humans have anti-Ad5 neutralising antibodies that can impair the immunological potency of such vaccines. Here we show that most other human Adenoviruses from rare serotypes are far less potent as vaccine vectors than Ad5 in mice and non-human primates, casting doubt on their potential efficacy in humans. To identify novel vaccine carriers suitable for vaccine delivery in humans we isolated and sequenced over a thousand Adenovirus strains from chimpanzees (ChAd). Replication-defective vectors were generated from different ChAd serotypes and were screened for neutralization by human sera and for ability to grow in human cell lines already approved for clinical studies. Most importantly, we devised a screening strategy to rank the ChAd vectors by immunological potency in mice which predicts their immunogenicity in non-human primates and humans. The vectors studied varied by up to a thousand-fold in potency for CD8 T cell induction in mice. Two of the most potent ChAd vectors were selected for clinical studies as carriers for Malaria and Hepatitis C virus (HCV) genetic vaccines. These ChAd vectors were found to be safe and immunologically potent in Phase I clinical trials thereby validating our screening approach. The ChAd vectors that we have developed represent a large collection of non cross-reactive, potent vectors that can be exploited for diverse vaccine strategies. |
| Databáze: | OpenAIRE |
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