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A Novel Vaccine Strategy Employing Serologically Different Chimpanzee Adenoviral Vectors for the Prevention of HIV-1 and HCV Coinfection

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 modifie...

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Autores principales: 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, Gardiner, Clair M., Bannan, Ciaran, Bergin, Colm, Hoffmann, Matthias, Turner, Bethany, Nicosia, Alfredo, Folgori, Antonella, Hanke, Tomáš, Barnes, Eleanor, Dorrell, Lucy
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6346592/
https://www.ncbi.nlm.nih.gov/pubmed/30713538
http://dx.doi.org/10.3389/fimmu.2018.03175
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author 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
Gardiner, Clair M.
Bannan, Ciaran
Bergin, Colm
Hoffmann, Matthias
Turner, Bethany
Nicosia, Alfredo
Folgori, Antonella
Hanke, Tomáš
Barnes, Eleanor
Dorrell, Lucy
author_facet 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
Gardiner, Clair M.
Bannan, Ciaran
Bergin, Colm
Hoffmann, Matthias
Turner, Bethany
Nicosia, Alfredo
Folgori, Antonella
Hanke, Tomáš
Barnes, Eleanor
Dorrell, Lucy
author_sort Hartnell, Felicity
collection PubMed
description 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 × 10(10) vp] and MVA-NSmut [2 × 10(8) pfu] at weeks 0 and 8, respectively; 8 received ChAdV63.HIVconsv [5 × 10(10) vp] and MVA.HIVconsv [2 × 10(8) pfu] at the same interval; 16 were co-primed with ChAd3-NSmut [2.5 × 10(10) vp] and ChAdV63.HIVconsv [5 × 10(10) vp] followed at week 8 by MVA-NSmut and MVA.HIVconsv [both 1 × 10(8) 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)/10(6) 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/10(6) 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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spelling pubmed-63465922019-02-01 A Novel Vaccine Strategy Employing Serologically Different Chimpanzee Adenoviral Vectors for the Prevention of HIV-1 and HCV Coinfection 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 Gardiner, Clair M. Bannan, Ciaran Bergin, Colm Hoffmann, Matthias Turner, Bethany Nicosia, Alfredo Folgori, Antonella Hanke, Tomáš Barnes, Eleanor Dorrell, Lucy Front Immunol Immunology 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 × 10(10) vp] and MVA-NSmut [2 × 10(8) pfu] at weeks 0 and 8, respectively; 8 received ChAdV63.HIVconsv [5 × 10(10) vp] and MVA.HIVconsv [2 × 10(8) pfu] at the same interval; 16 were co-primed with ChAd3-NSmut [2.5 × 10(10) vp] and ChAdV63.HIVconsv [5 × 10(10) vp] followed at week 8 by MVA-NSmut and MVA.HIVconsv [both 1 × 10(8) 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)/10(6) 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/10(6) 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 Frontiers Media S.A. 2019-01-18 /pmc/articles/PMC6346592/ /pubmed/30713538 http://dx.doi.org/10.3389/fimmu.2018.03175 Text en Copyright © 2019 Hartnell, Brown, Capone, Kopycinski, Bliss, Makvandi-Nejad, Swadling, Ghaffari, Cicconi, Del Sorbo, Sbrocchi, Esposito, Vassilev, Marriott, Gardiner, Bannan, Bergin, Hoffmann, Turner, Nicosia, Folgori, Hanke, Barnes and Dorrell. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
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
Gardiner, Clair M.
Bannan, Ciaran
Bergin, Colm
Hoffmann, Matthias
Turner, Bethany
Nicosia, Alfredo
Folgori, Antonella
Hanke, Tomáš
Barnes, Eleanor
Dorrell, Lucy
A Novel Vaccine Strategy Employing Serologically Different Chimpanzee Adenoviral Vectors for the Prevention of HIV-1 and HCV Coinfection
title A Novel Vaccine Strategy Employing Serologically Different Chimpanzee Adenoviral Vectors for the Prevention of HIV-1 and HCV Coinfection
title_full A Novel Vaccine Strategy Employing Serologically Different Chimpanzee Adenoviral Vectors for the Prevention of HIV-1 and HCV Coinfection
title_fullStr A Novel Vaccine Strategy Employing Serologically Different Chimpanzee Adenoviral Vectors for the Prevention of HIV-1 and HCV Coinfection
title_full_unstemmed A Novel Vaccine Strategy Employing Serologically Different Chimpanzee Adenoviral Vectors for the Prevention of HIV-1 and HCV Coinfection
title_short A Novel Vaccine Strategy Employing Serologically Different Chimpanzee Adenoviral Vectors for the Prevention of HIV-1 and HCV Coinfection
title_sort novel vaccine strategy employing serologically different chimpanzee adenoviral vectors for the prevention of hiv-1 and hcv coinfection
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6346592/
https://www.ncbi.nlm.nih.gov/pubmed/30713538
http://dx.doi.org/10.3389/fimmu.2018.03175
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