| Affiliation: | 1. The Jenner Institute Laboratories, University of Oxford, Old Road Campus Research Building, Oxford, UK;2. MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, The John Radcliffe, Oxford, UK;3. IAVI Human Immunology Laboratory, Imperial College, London, UK;4. Centre for Clinical Vaccinology and Tropical Medicine, The Jenner Institute, University of Oxford, Churchill Hospital, Oxford, UK;5. Current address: Institut Pasteur du Laos, Vientiane, Laos People''s Democratic Republic;6. Current address: Medical Microbiology and Immunology, Li Ka Shing Institute of Virology, 6–096 Katz Centre for Health Research, Edmonton, Alberta, Canada;7. Clinical Biomanufacturing Facility, University of Oxford, Churchill Hospital, Oxford, UK;8. Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA;9. Okairos, Rome, Italy;10. CEINGE, Naples, Italy;11. Department of Biochemistry and Medical Biotechnology, University of Naples Federico II, Naples, Italy |
| Abstract: | Virus diversity and escape from immune responses are the biggest challenges to the development of an effective vaccine against HIV-1. We hypothesized that T-cell vaccines targeting the most conserved regions of the HIV-1 proteome, which are common to most variants and bear fitness costs when mutated, will generate effectors that efficiently recognize and kill virus-infected cells early enough after transmission to potentially impact on HIV-1 replication and will do so more efficiently than whole protein-based T-cell vaccines. Here, we describe the first-ever administration of conserved immunogen vaccines vectored using prime-boost regimens of DNA, simian adenovirus and modified vaccinia virus Ankara to uninfected UK volunteers. The vaccine induced high levels of effector T cells that recognized virus-infected autologous CD4+ cells and inhibited HIV-1 replication by up to 5.79 log10. The virus inhibition was mediated by both Gag- and Pol- specific effector CD8+ T cells targeting epitopes that are typically subdominant in natural infection. These results provide proof of concept for using a vaccine to target T cells at conserved epitopes, showing that these T cells can control HIV-1 replication in vitro. |
