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 TITLE=A Novel Vaccine Strategy Employing Serologically Different Chimpanzee Adenoviral Vectors for the Prevention of HIV-1 and HCV Coinfection JOURNAL=Frontiers in Immunology VOLUME=9 YEAR=2019 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2018.03175 DOI=10.3389/fimmu.2018.03175 ISSN=1664-3224 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