title: Novel Conserved-region T-cell Mosaic Vaccine With High Global HIV-1 Coverage Is Recognized by Protective Responses in Untreated Infection.
abstract: An effective human immunodeficiency virus type 1 (HIV-1) vaccine is the best solution for halting the acquired immune deficiency syndrome epidemic. Here, we describe the design and preclinical immunogenicity of T-cell vaccine expressing novel immunogens tHIVconsvX, vectored by DNA, simian (chimpanzee) adenovirus, and poxvirus modified vaccinia virus Ankara (MVA), a combination highly immunogenic in humans. The tHIVconsvX immunogens combine the three leading strategies for elicitation of effective CD8(+) T cells: use of regions of HIV-1 proteins functionally conserved across all M group viruses (to make HIV-1 escape costly on viral fitness), inclusion of bivalent complementary mosaic immunogens (to maximize global epitope matching and breadth of responses, and block common escape paths), and inclusion of epitopes known to be associated with low viral load in infected untreated people (to induce field-proven protective responses). tHIVconsvX was highly immunogenic in two strains of mice. Furthermore, the magnitude and breadth of CD8(+) T-cell responses to tHIVconsvX-derived peptides in treatment-naive HIV-1(+) patients significantly correlated with high CD4(+) T-cell count and low viral load. Overall, the tHIVconsvX design, combining the mosaic and conserved-region approaches, provides an indisputably better coverage of global HIV-1 variants than previous T-cell vaccines. These immunogens delivered in a highly immunogenic framework of adenovirus prime and MVA boost are ready for clinical development.
authors.affiliation: The Jenner Institute, University of Oxford, Roosevelt Drive, Oxford, UK.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Ondondo
authors.affiliation: Center for AIDS Research, Kumamoto University, Kumamoto, Japan.
authors.forename: Hayato
authors.initials: H
authors.lastname: Murakoshi
authors.affiliation: The Jenner Institute, University of Oxford, Roosevelt Drive, Oxford, UK.|Current address: Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
authors.forename: Genevieve
authors.initials: G
authors.lastname: Clutton
authors.affiliation: The Jenner Institute, University of Oxford, Roosevelt Drive, Oxford, UK.
authors.forename: Sultan
authors.initials: S
authors.lastname: Abdul-Jawad
authors.affiliation: The Jenner Institute, University of Oxford, Roosevelt Drive, Oxford, UK.
authors.forename: Edmund G-T
authors.initials: EG
authors.lastname: Wee
authors.affiliation: Center for AIDS Research, Kumamoto University, Kumamoto, Japan.|AIDS Clinical Center, National Center for Global Health and Medicine, Tokyo, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Gatanaga
authors.affiliation: Center for AIDS Research, Kumamoto University, Kumamoto, Japan.|AIDS Clinical Center, National Center for Global Health and Medicine, Tokyo, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Oka
authors.affiliation: NDM Research Building, University of Oxford, Oxford, UK.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: McMichael
authors.affiliation: Center for AIDS Research, Kumamoto University, Kumamoto, Japan.|International Research Center for Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Takiguchi
authors.affiliation: Los Alamo National Laboratory, Theoretical Biology and Biophysics, Los Alamos, New Mexico, USA.|The New Mexico Consortium, Los Alamos, New Mexico, USA.
authors.forename: Bette
authors.initials: B
authors.lastname: Korber
authors.affiliation: The Jenner Institute, University of Oxford, Roosevelt Drive, Oxford, UK.|International Research Center for Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Tomáš
authors.initials: T
authors.lastname: Hanke
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D000261:Adenoviruses, Simian / Q000276:immunology; D000818:Animals; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology* / Q000628:therapy*; D015497:HIV-1 / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D014616:Vaccinia virus / Q000276:immunology; D019562:Viral Load
chemical_list: D016915:AIDS Vaccines