Oral Abstract Session 01 - Global HIV Vaccine Enterprise

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POSTERS Posters Topic 11: T Cell Immunity P11.15 The Impact of HLA-Cw*12:02 on Control of HIV-1 Infection M. Koyanagi 1 , K. Honda 1 , T. Chikata 1 , T. Akahoshi 1 , H. Murakoshi 1 , H. Gatanaga 2 , S. Oka 2 , M. Takiguchi 1 1 Center for AIDS Research, Kumamoto University, Kumamoto, Japan; 2 AIDS Clinical Center, National Center for Global Health and Medicine, Tokyo, Japan Background: Previous studies have demonstrated that higher HLA-C expression, which is determined through a single nucleotide polymorphism 35 kb upstream and the variation within the 3’ untranslated region of the HLA-C locus, associate with slow progression of HIV-1-infected disease. Although HLA-C plays important roles in presenting antigens to CTLs or a ligand for inhibitory killer cell Ig-like receptors (KIR), the role of HLA-C-restricted CTL and NK cells in the control of HIV-1 is still unclear. Our recent study of chronically HIV-1 infected Japanese cohort showed that the HLA-B*52:01-Cw*12:02 haplotype was significantly associated with lower viral load. In this study, we investigated whether HLA-Cw*12:02-restricted CTLs or NK cells via KIR have a significant impact on viraemic control. Methods: We sequenced Pol, Gag and Nef from 400 chronically HIV- 1 clade B-infected treatment-naïve Japanese individuals and then analyzed amino acid polymorphisms associated with HLA-B*52:01- Cw*12:02 haplotype using Fisher’s exact test. Next we performed intracellular IFNg staining or IFNg ELISPOT assay to detect CTL responses to the peptides including those polymorphisms. Results: We found 9 amino acid polymorphisms significantly associated with HLA-B*52:01-Cw*12:02 haplotype (p
Topic 11: T Cell Immunity P11.17 Recombinant DNA/MVA/ChAdV-63-Elicited T Cells Specific for Conserved Regions of the HIV- 1 Proteome Recognize HIV-1 Infected Cells and Suppress HIV-1 T. Ahmed 1 , N. Borthwick 1 , H. Yang 1 , G. Hancock 1 , L. Yorke 1 , U. Ebrahimsa 1 , A. Rose 1 , A. Black 1 , E. Hayton 1 , A. McMichael 1 , L. Dorrell 1 , T. Hanke 1 1 Oxford University, Oxford, United Kingdom (Great Britain) Background: Currently, immunogenicity assessments of candidate HIV-1 vaccines in human clinical trials rely on the use of peptides for sensitization of target cells. However, employment of HIV-1-infected cells provides more informative and relevant in vitro readouts of HIV-1 recognition. Methods: A viral suppression assay (VSA) was developed to assess CD8+ T cell responses to infected autologous CD4+ targets using HIV-1 p24 levels as measured by flow cytometry and ELISA. In parallel, we also investigated live virus infected cells for restimulation of vaccine elicited T cells in an IFN-γ ELISpot assay. Results: HIV-1 infection kinetics is influenced by the multiplicity of infection (MOI) used to infect autologous CD4+ cells, with rapid kinetics observed at higher MOIs. For HIV-1 BaL optimal infection of autologous CD4+ cells was achieved at MOI of 0.05. In the VSA, HIV-1 BaL virus replication was shown to be sensitive to the chemokines MIP-1α and RANTES added in the absence of effector cells. Pre-activated effector cells indicated increased non-specific background suppression in healthy controls, which was reduced following a prolonged rest before co-culture with autologous CD4+ targets, but led to marked proliferation of the CD8+ T cell effectors. Preliminary investigations in vaccinees show that HIV-1 suppression mediated by CD8+ T cells can be detected in vitro following vaccination and that P24 ELISA has higher sensitivity than flow cytometry. As an alternative to the VSA, an IFN-γ ELISpot assay has also been optimized for the use of autologous HIV-1-infected CD4+ cells. Using both of the above assays, preliminary characterization of T cell responses induced in volunteers receiving pSG2.HIVconsv DNA, MVA.HIVconsv and ChAdV63.HIVconsv vaccines will be shown. Conclusion: Two assays employing HIV-1 infected target cells were standardised and employed to characterize responses elicited in participants of the HIV-1 vaccine trial HIVCORE002 in Oxford, UK. P11.18 AIDS Vaccine 2012 Posters Breadth or Conservation Score (CS): Which Is More Important for HIV-1 T Cell Based Vaccine Immunogen Design? P. Kunwar 1 , N.R. Hawkins 2 , X. Yu 2 , Y. Liu 3 , A. Collier 4 , E.E. Gabriel 2 , T. Hertz 2 , H. Horton 5 1 University of Washington / Seattle Biomedical Research Institute, Seattle, WA, USA; 2 Statistical Center for HIV/ AIDS Research & Prevention (SCHARP), Seattle, WA, USA; 3 Department of Microbiology, University of Washington, Seattle, WA, USA; 4 Department of Medicine, University of Washington, Seattle, WA, USA; 5 Seattle Biomedical Research Institute, Seattle, WA, USA Background: One of the greatest challenges to develop an efficacious HIV vaccine is the enormous diversity of HIV-1. To tackle this problem, T cells based vaccine approaches have come up with two main camps: the mosaic immunogen camp: increasing the breadth of vaccine-induced responses, and the conserved immunogen camp: targeting vaccine-induced T-cell responses only to highly conserved viral regions. While both approaches are theoretically sound, there is no current data suggesting that either approach will be successful in inducing T cells with superior antiviral efficacy. Here we analyzed T cell responses elicited during early HIV-1 infection, to address the question whether CS of targeted epitopes and breadth of T cell responses play an important role in viral control. Methods: Using IFN-γ ELISpot, we comprehensively mapped T cell epitope specificities recognized by 24 ART-naïve individuals during early infection. We identified CS of targeted epitopes, where the CS is defined as the proportion of random HIV-1 group M amino acid sequences in the LANL database that include the epitope. We used a prediction model to impute the viral load (VL) set-point using the first available VL as a predictor for subjects lacking VL set-point. We further evaluated the association between the CS of the targeted epitopes and breadth of T cell responses to the individuals’ VL set-point. Results: The breadth of CD8+ T cell responses inversely correlated with VL set-point (r=-0.46, p=0.025). Subjects possessing CD8+ T cells recognizing at least one conserved epitope had a lower VL set-point compared to those recognizing only variable epitopes (p=0.093). Conclusion: Breadth and CS of HIV-specific CD8+ T cells elicited during early infection are both important for controlling viral replication in vivo. Rationale design of immunization approaches should aim at eliciting a greater breadth of CD8+ T cell to conserved epitopes. This project is funded by NIH grant#R01AI090783 225 POSTERS
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AIDS Vaccine 2012 PROGRAM AT A GLAN
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AIDS Vaccine 2012 Partners www.alli
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CONFERENCE ORGANIZERS Conference Or
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CONFERENCE ORGANIZERS Conference Or
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SCHOLARSHIP RECIPIENTS Awards and S
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SCHOLARSHIP RECIPIENTS Awards and S
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PROGRAM / MONDAY 2 Program Monday,
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PROGRAM / MONDAY 4 Program 11:00 -
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PROGRAM / TUESDAY 10 Program Tuesda
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PROGRAM / TUESDAY 12 Program 11:45
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PROGRAM / TUESDAY 14 Program 13:30
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PROGRAM / TUESDAY 16 Program Poster
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PROGRAM / TUESDAY 18 Program AIDS V
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PROGRAM / WEDNESDAY 20 Program Wedn
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22 AIDS Vaccine 2012
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PLENARY SESSIONS 24 Plenary Session
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SYMPOSIA SESSIONS 30 Symposia Sessi
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ORAL ABSTRACT SESSIONS 54 Oral Abst
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92 AIDS Vaccine 2012
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POSTERS 94 AIDS Vaccine 2012
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POSTERS 96 Posters Topic 1: Adjuvan
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POSTERS 98 Posters Topic 1: Adjuvan
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POSTERS Posters Topic 1: Adjuvants,
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POSTERS Posters Topic 2: Animal Mod
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POSTERS Posters Topic 3: B Cell Imm
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POSTERS Posters Topic 4: Clinical V
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POSTERS Posters Topic 5: HIV Transm
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POSTERS Posters Topic 12: Vaccine C
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POSTERS Posters Topic 13: Pediatric
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AUTHOR INDEX Author Index Brander,
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AUTHOR INDEX Author Index Guan, Y .
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AUTHOR INDEX Author Index Lucas, J.
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AUTHOR INDEX Author Index Quinn, T
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AUTHOR INDEX Author Index Wendel-Ha
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Notes 288
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Notes 290
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Poster Session 1 - Monday, 10 Septe
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Oral Abstract Session 01 - Global HIV Vaccine Enterprise

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