Publication
A Novel Vaccine Strategy Employing Serologically Different Chimpanzee Adenoviral Vectors for the Prevention of HIV-1 and HCV Coinfection
Journal Paper/Review - Jan 18, 2019
Hartnell Felicity, Marriott Paula, Gardiner Clair M, Bannan Ciaran, Bergin Colm, Hoffmann Matthias, Turner Bethany, Nicosia Alfredo, Folgori Antonella, Hanke Tomáš, Barnes Eleanor, Vassilev Ventzislav, Esposito Ilaria, Brown Anthony, Capone Stefania, Kopycinski Jakub, Bliss Carly, Makvandi-Nejad Shokouh, Swadling Leo, Ghaffari Emma, Cicconi Paola, Del Sorbo Mariarosaria, Sbrocchi Roberta, Dorrell Lucy
Units
PubMed
Doi
Citation
Type
Journal
Publication Date
Issn Electronic
Pages
Brief description/objective
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. 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 vp] and MVA-NSmut [2 × 10 pfu] at weeks 0 and 8, respectively; 8 received ChAdV63.HIVconsv [5 × 10 vp] and MVA.HIVconsv [2 × 10 pfu] at the same interval; 16 were co-primed with ChAd3-NSmut [2.5 × 10 vp] and ChAdV63.HIVconsv [5 × 10 vp] followed at week 8 by MVA-NSmut and MVA.HIVconsv [both 1 × 10 pfu]. Immunogenicity was assessed using peptide pools in ELISpot and intracellular cytokine assays. Vaccine-induced whole blood transcriptome changes were assessed by microarray analysis. 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 PBMC for single and combined HCV vaccinations, respectively ( = 0.8). Median (IQR) peak responses to HIVconsv were 1,305 (1,095-4,967) and 1,005 (169-2,482) SFC/10 PBMC for single and combined HIV-1 vaccinations, respectively ( = 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. 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. https://clinicaltrials.gov, identifier: NCT02362217.