title: Characterization of T-cell responses to conserved regions of the HIV-1 proteome in BALB/c mice.
abstract: A likely requirement for a protective vaccine against human immunodeficiency virus type 1 (HIV-1)/AIDS is, in addition to eliciting antibody responses, induction of effective T cells. To tackle HIV-1 diversity by T-cell vaccines, we designed an immunogen, HIVconsv, derived from the most functionally conserved regions of the HIV-1 proteome and demonstrated its high immunogenicity in humans and rhesus macaques when delivered by regimens combining plasmid DNA, nonreplicating simian (chimpanzee) adenovirus ChAdV-63, and nonreplicating modified vaccinia virus Ankara (MVA) as vectors. Here, we aimed to increase the decision power for iterative improvements of this vaccine strategy in the BALB/c mouse model. First, we found that prolonging the period after the ChAdV63.HIVconsv prime up to 6 weeks increased the frequencies of HIV-1-specific, gamma interferon (IFN-γ)-producing T cells induced by the MVA.HIVconsv boost. Induction of strong responses allowed us to map comprehensively the H-2(d)-restricted T-cell responses to these regions and identified 8 HIVconsv peptides, of which three did not contain a previously described epitope and were therefore considered novel. Induced effector T cells were oligofunctional and lysed sensitized targets in vitro. Our study therefore provides additional tools for studying and optimizing vaccine regimens in this commonly used small animal model, which will in turn guide vaccine improvements in more expensive nonhuman primate and human clinical trials.
authors.affiliation: The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Ondondo
authors.affiliation: The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
authors.forename: Sultan
authors.initials: S
authors.lastname: Abdul-Jawad
authors.affiliation: MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, Nuffield Department of Medicine, University of Oxford, The John Radcliffe, Oxford, United Kingdom.
authors.forename: Anne
authors.initials: A
authors.lastname: Bridgeman
authors.affiliation: The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, Nuffield Department of Medicine, University of Oxford, The John Radcliffe, Oxford, United Kingdom tomas.hanke@ndm.ox.ac.uk.
authors.forename: Tomáš
authors.initials: T
authors.lastname: Hanke
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology* / Q000302:isolation & purification; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D017124:Conserved Sequence / Q000276:immunology*; D004337:Drug Carriers; D018984:Epitopes, T-Lymphocyte / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D005260:Female; D005822:Genetic Vectors; D015497:HIV-1 / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism*; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014616:Vaccinia virus / Q000235:genetics; D014764:Viral Proteins / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D004337:Drug Carriers; D018984:Epitopes, T-Lymphocyte; D011994:Recombinant Proteins; D014764:Viral Proteins; D007371:Interferon-gamma