A novel vaccine strategy employing serologically different chimpanzee adenoviral vectors for the prevention of HIV-1 and HCV coinfection
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2019Author:
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Hartnell, F., Brown, A., Capone, S., Kopycinski, J., Bliss, C., Makvandi-Nejad, S., Swadling, L., Ghaffari, E., Cicconi, P., Sorbo, M.D., Sbrocchi, R., Esposito, I., Vassilev, V., Marriott, P., Gardiner, C.M., Bannan, C., Bergin, C. , Hoffmann, M., Turner, B., Nicosia, A., Folgori, A., Hanke, T., Barnes, E. & Dorrell, L., A novel vaccine strategy employing serologically different chimpanzee adenoviral vectors for the prevention of HIV-1 and HCV coinfection, Frontiers in Immunology, 10, JAN, 2019Download Item:
Abstract:
Background: Nearly 3 million people worldwide are coinfected with HIV and HCV. Affordable strategies for prevention are needed. We developed a novel vaccination regimen involving replication-defective and serologically distinct chimpanzee adenovirus (ChAd3, ChAd63) vector priming followed by modified vaccinia Ankara (MVA) boosts, for simultaneous delivery of HCV non-structural (NSmut) and HIV-1 conserved (HIVconsv) region immunogens.
Methods: We conducted a phase I trial in which 33 healthy volunteers were sequentially enrolled and vaccinated via the intramuscular route as follows: 9 received ChAd3-NSmut [2.5 × 1010 vp] and MVA-NSmut [2 × 108 pfu] at weeks 0 and 8, respectively; 8 received ChAdV63.HIVconsv [5 × 1010 vp] and MVA.HIVconsv [2 × 108 pfu] at the same interval; 16 were co-primed with ChAd3-NSmut [2.5 × 1010 vp] and ChAdV63.HIVconsv [5 × 1010 vp] followed at week 8 by MVA-NSmut and MVA.HIVconsv [both 1 × 108 pfu]. Immunogenicity was assessed using peptide pools in ex vivo ELISpot and intracellular cytokine assays. Vaccine-induced whole blood transcriptome changes were assessed by microarray analysis.
Results: All vaccines were well tolerated and no vaccine-related serious adverse events occurred. Co-administration of the prime-boost vaccine regimens induced high magnitude and broad T cell responses that were similar to those observed following immunization with either regimen alone. Median (interquartile range, IQR) peak responses to NSmut were 3,480 (2,728–4,464) and 3,405 (2,307–7,804) spot-forming cells (SFC)/106 PBMC for single and combined HCV vaccinations, respectively (p = 0.8). Median (IQR) peak responses to HIVconsv were 1,305 (1,095–4,967) and 1,005 (169–2,482) SFC/106 PBMC for single and combined HIV-1 vaccinations, respectively (p = 0.5). Responses were maintained above baseline to 34 weeks post-vaccination. Intracellular cytokine analysis indicated that the responding populations comprised polyfunctional CD4+ and CD8+ T cells. Canonical pathway analysis showed that in the single and combined vaccination groups, pathways associated with antiviral and innate immune responses were enriched for upregulated interferon-stimulated genes 24 h after priming and boosting vaccinations.
Conclusions: Serologically distinct adenoviral vectors encoding HCV and HIV-1 immunogens can be safely co-administered without reducing the immunogenicity of either vaccine. This provides a novel strategy for targeting these viruses simultaneously and for other pathogens that affect the same populations.
Clinical trial registration: https://clinicaltrials.gov, identifier: NCT02362217
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https://www.frontiersin.org/articles/10.3389/fimmu.2018.03175/fullhttp://hdl.handle.net/2262/91598
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http://people.tcd.ie/gardinec
Author: Gardiner, Clair; Hartnell, Felicity; Brown, Anthony; Capone, Stefania; Kopycinski, Jakub; Bliss, Carly; Makvandi-Nejad, Shokouh; Swadling, Leo; Ghaffari, Emma; Cicconi, Paola; Del Sorbo, Mariarosaria; Sbrocchi, Roberta; Esposito, Ilaria; Vassilev, Ventzislav; Marriott, Paula; Bannan, Ciaran; Bergin, Colm; Hoffmann, Matthias; Turner, Bethany; Nicosia, Alfredo; Folgori, Antonella; Hanke, Tomáš; Barnes, Eleanor; Dorrell, Lucy
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https://www.frontiersin.org/articles/10.3389/fimmu.2018.03175/fullhttp://hdl.handle.net/2262/91598
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Frontiers in Immunology;10;
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HIV-1, Hepatitis C, Vaccine, Coadministration, Clinical trial, Conserved region, Non-structural protein, Transciptomics analysisDOI:
http://dx.doi.org/10.3389/fimmu.2018.03175Metadata
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