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Open Access 01-12-2011 | Research

Definition of the viral targets of protective HIV-1-specific T cell responses

Authors: Beatriz Mothe, Anuska Llano, Javier Ibarrondo, Marcus Daniels, Cristina Miranda, Jennifer Zamarreño, Vanessa Bach, Rosario Zuniga, Susana Pérez-Álvarez, Christoph T Berger, Maria C Puertas, Javier Martinez-Picado, Morgane Rolland, Marilu Farfan, James J Szinger, William H Hildebrand, Otto O Yang, Victor Sanchez-Merino, Chanson J Brumme, Zabrina L Brumme, David Heckerman, Todd M Allen, James I Mullins, Guadalupe Gómez, Philip J Goulder, Bruce D Walker, Jose M Gatell, Bonaventura Clotet, Bette T Korber, Jorge Sanchez, Christian Brander

Published in: Journal of Translational Medicine | Issue 1/2011

Abstract

Background

The efficacy of the CTL component of a future HIV-1 vaccine will depend on the induction of responses with the most potent antiviral activity and broad HLA class I restriction. However, current HIV vaccine designs are largely based on viral sequence alignments only, not incorporating experimental data on T cell function and specificity.

Methods

Here, 950 untreated HIV-1 clade B or -C infected individuals were tested for responses to sets of 410 overlapping peptides (OLP) spanning the entire HIV-1 proteome. For each OLP, a "protective ratio" (PR) was calculated as the ratio of median viral loads (VL) between OLP non-responders and responders.

Results

For both clades, there was a negative relationship between the PR and the entropy of the OLP sequence. There was also a significant additive effect of multiple responses to beneficial OLP. Responses to beneficial OLP were of significantly higher functional avidity than responses to non-beneficial OLP. They also had superior in-vitro antiviral activities and, importantly, were at least as predictive of individuals' viral loads than their HLA class I genotypes.

Conclusions

The data thus identify immunogen sequence candidates for HIV and provide an approach for T cell immunogen design applicable to other viral infections.

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Brander C, Frahm N, Walker B: Host immunity and viral diversity in HIV vaccine design. Current Opinion Immunol. 2006, 18: 1-8. 10.1016/j.coi.2005.11.016.CrossRef

Kiepiela P, Leslie AJ, Honeyborne I, Ramduth D, Thobakgale C, Chetty S, Rathnavalu P, Moore C, Pfafferott KJ, Hilton L, Zimbwa P, Moore S, Allen T, Brander C, Addo MM, Altfeld M, James I, Mallal S, Bunce M, Barber LD, Szinger J, Day C, Klenerman P, Mullins J, Korber B, Coovadia HM, Walker BD, Goulder PJ: Dominant influence of HLA-B in mediating the potential co-evolution of HIV and HLA. Nature. 2004, 432 (7018): 769-775. 10.1038/nature03113.CrossRefPubMed

Frahm N, Adams S, Kiepiela P, Linde CH, Hewitt HS, Lichterfeld M, Sango K, Brown NV, Pae E, Wurcel AG, Altfeld M, Feeney ME, Allen TM, Roach T, St John MA, Daar ES, Rosenberg E, Korber B, Marincola F, Walker BD, Goulder PJ, Brander C: HLA-B63 presents HLA-B57/B58-restricted cytotoxic T-lymphocyte epitopes and is associated with low human immunodeficiency virus load. J Virol. 2005, 79 (16): 10218-10225. 10.1128/JVI.79.16.10218-10225.2005.PubMedCentralCrossRefPubMed

Frahm N, Kiepiela P, Adams S, Linde CH, Hewitt HS, Sango K, Feeney ME, Addo MM, Lichterfeld M, Lahaie MP, Pae E, Wurcel AG, Roach T, St John MA, Altfeld M, Marincola FM, Moore C, Mallal S, Carrington M, Heckerman D, Allen TM, Mullins JI, Korber BT, Goulder PJ, Walker BD, Brander C: Control of human immunodeficiency virus replication by cytotoxic T lymphocytes targeting subdominant epitopes. Nat Immunol. 2006, 7 (2): 173-178. 10.1038/ni1281.CrossRefPubMed

Ngumbela KC, Day CL, Mncube Z, Nair K, Ramduth D, Thobakgale C, Moodley E, Reddy S, de Pierres C, Mkhwanazi N, Bishop K, van der Stok M, Ismail N, Honeyborne I, Crawford H, Kavanagh DG, Rousseau C, Nickle D, Mullins J, Heckerman D, Korber B, Coovadia H, Kiepiela P, Goulder PJ, Walker BD: Targeting of a CD8 T cell env epitope presented by HLA-B*5802 is associated with markers of HIV disease progression and lack of selection pressure. AIDS Res Hum Retroviruses. 2008, 24 (1): 72-82. 10.1089/aid.2007.0124.CrossRefPubMed

Brockman MA, Schneidewind A, Lahaie M, Schmidt A, Miura T, Desouza I, Ryvkin F, Derdeyn CA, Allen S, Hunter E, Mulenga J, Goepfert PA, Walker BD, Allen TM: Escape and compensation from early HLA-B57-mediated cytotoxic T-lymphocyte pressure on human immunodeficiency virus type 1 Gag alter capsid interactions with cyclophilin A. J Virol. 2007, 81 (22): 12608-12618. 10.1128/JVI.01369-07.PubMedCentralCrossRefPubMed

Schneidewind A, Brockman MA, Yang R, Adam RI, Li B, Le Gall S, Rinaldo CR, Craggs SL, Allgaier RL, Power KA, Kuntzen T, Tung CS, LaBute MX, Mueller SM, Harrer T, McMichael AJ, Goulder PJ, Aiken C, Brander C, Kelleher AD, Allen TM: Escape from the dominant HLA-B27-restricted cytotoxic T-lymphocyte response in Gag is associated with a dramatic reduction in human immunodeficiency virus type 1 replication. J Virol. 2007, 81 (22): 12382-12393. 10.1128/JVI.01543-07.PubMedCentralCrossRefPubMed

Leslie A, Price DA, Mkhize P, Bishop K, Rathod A, Day C, Crawford H, Honeyborne I, Asher TE, Luzzi G, Edwards A, Rousseau CM, Mullins JI, Tudor-Williams G, Novelli V, Brander C, Douek DC, Kiepiela P, Walker BD, Goulder PJ: Differential selection pressure exerted on HIV by CTL targeting identical epitopes but restricted by distinct HLA alleles from the same HLA supertype. J Immunol. 2006, 177 (7): 4699-4708.CrossRefPubMed

Iversen AK, Stewart-Jones G, Learn GH, Christie N, Sylvester-Hviid C, Armitage AE, Kaul R, Beattie T, Lee JK, Li Y, Chotiyarnwong P, Dong T, Xu X, Luscher MA, MacDonald K, Ullum H, Klarlund-Pedersen B, Skinhoj P, Fugger L, Buus S, Mullins JI, Jones EY, van der Merwe PA, McMichael AJ: Conflicting selective forces affect T cell receptor contacts in an immunodominant human immunodeficiency virus epitope. Nat Immunol. 2006, 7 (2): 179-189. 10.1038/ni1298.CrossRefPubMed

10.

Kijak GH, Currier JR, Tovanabutra S, Cox JH, Michael NL, Wegner SA, Birx DL, McCutchan FE: Lost in translation: implications of HIV-1 codon usage for immune escape and drug resistance. AIDS Rev. 2004, 6 (1): 54-60.PubMed

11.

Price DA, West SM, Betts MR, Ruff LE, Brenchley JM, Ambrozak DR, Edghill-Smith Y, Kuroda MJ, Bogdan D, Kunstman K, Letvin NL, Franchini G, Wolinsky SM, Koup RA, Douek D: T cell receptor recognition motifs govern immune escape patterns in acute SIV infection. Immunity. 2004

12.

Bihl F, Frahm N, Di Giammarino L, Sidney J, John M, Yusim K, Woodberry T, Sango K, Hewitt HS, Henry L, Linde CH, Chisholm JV, Zaman TM, Pae E, Mallal S, Walker BD, Sette A, Korber BT, Heckerman D, Brander C: Impact of HLA-B alleles, epitope binding affinity, functional avidity, and viral coinfection on the immunodominance of virus-specific CTL responses. J Immunol. 2006, 176 (7): 4094-4101.CrossRefPubMed

13.

Yerly D, Heckerman D, Allen TM, Chisholm JV, Faircloth K, Linde CH, Frahm N, Timm J, Pichler WJ, Cerny A, Brander C: Increased cytotoxic T-lymphocyte epitope variant cross-recognition and functional avidity are associated with hepatitis C virus clearance. J Virol. 2008, 82 (6): 3147-3153. 10.1128/JVI.02252-07.PubMedCentralCrossRefPubMed

14.

Zuñiga R, Lucchetti A, Galvan P, Sanchez S, Sanchez C, Hernandez A, Sanchez H, Frahm N, Linde C, Hewitt HS, Hildebrand WH, Altfeld M, Allen T, Walker B, Korber B, Leitner T, Sanchez J, Brander C: Relative dominance of Gag p24 specific CTL is associated with HIV control. J Virology. 2006, 80: 3122-3125. 10.1128/JVI.80.6.3122-3125.2006.PubMedCentralCrossRefPubMed

15.

Masemola A, Mashishi T, Khoury G, Mohube P, Mokgotho P, Vardas E, Colvin M, Zijenah L, Katzenstein D, Musonda R, Allen S, Kumwenda N, Taha T, Gray G, McIntyre J, Karim SA, Sheppard HW, Gray CM: Hierarchical targeting of subtype C human immunodeficiency virus type 1 proteins by CD8+ T cells: correlation with viral load. J Virol. 2004, 78 (7): 3233-3243. 10.1128/JVI.78.7.3233-3243.2004.PubMedCentralCrossRefPubMed

16.

Kiepiela P, Ngumbela K, Thobakgale C, Ramduth D, Honeyborne I, Moodley E, Reddy S, de Pierres C, Mncube Z, Mkhwanazi N, Bishop K, van der Stok M, Nair K, Khan N, Crawford H, Payne R, Leslie A, Prado J, Prendergast A, Frater J, McCarthy N, Brander C, Learn GH, Nickle D, Rousseau C, Coovadia H, Mullins JI, Heckerman D, Walker BD, Goulder P: CD8+ T-cell responses to different HIV proteins have discordant associations with viral load. Nat Med. 2007, 13 (1): 46-53. 10.1038/nm1520.CrossRefPubMed

17.

Borghans JA, Molgaard A, de Boer RJ, Kesmir C: HLA alleles associated with slow progression to AIDS truly prefer to present HIV-1 p24. PLoS ONE. 2007, 2 (9): e920-10.1371/journal.pone.0000920.PubMedCentralCrossRefPubMed

18.

Sacha JB, Chung C, Rakasz EG, Spencer SP, Jonas AK, Bean AT, Lee W, Burwitz BJ, Stephany JJ, Loffredo JT, Allison DB, Adnan S, Hoji A, Wilson NA, Friedrich TC, Lifson JD, Yang OO, Watkins DI: Gag-specific CD8+ T lymphocytes recognize infected cells before AIDS-virus integration and viral protein expression. J Immunol. 2007, 178 (5): 2746-2754.PubMedCentralCrossRefPubMed

19.

Honeyborne I, Prendergast A, Pereyra F, Leslie A, Crawford H, Payne R, Reddy S, Bishop K, Moodley E, Nair K, van der Stok M, McCarthy N, Rousseau CM, Addo M, Mullins JI, Brander C, Kiepiela P, Walker BD, Goulder PJ: Control of human immunodeficiency virus type 1 is associated with HLA-B*13 and targeting of multiple gag-specific CD8+ T-cell epitopes. J Virol. 2007, 81 (7): 3667-3672. 10.1128/JVI.02689-06.PubMedCentralCrossRefPubMed

20.

Leslie AJ, Pfafferott KJ, Chetty P, Draenert R, Addo MM, Feeney M, Tang Y, Holmes EC, Allen T, Prado JG, Altfeld M, Brander C, Dixon C, Ramduth D, Jeena P, Thomas SA, St John A, Roach TA, Kupfer B, Luzzi G, Edwards A, Taylor G, Lyall H, Tudor-Williams G, Novelli V, Martinez-Picado J, Kiepiela P, Walker BD, Goulder PJ: HIV evolution: CTL escape mutation and reversion after transmission. Nat Med. 2004, 10 (3): 282-289. 10.1038/nm992.CrossRefPubMed

21.

Martinez-Picado J, Prado JG, Fry EE, Pfafferott K, Leslie A, Chetty S, Thobakgale C, Honeyborne I, Crawford H, Matthews P, Pillay T, Rousseau C, Mullins JI, Brander C, Walker BD, Stuart DI, Kiepiela P, Goulder P: Fitness cost of escape mutations in p24 Gag in association with control of human immunodeficiency virus type 1. J Virol. 2006, 80 (7): 3617-3623. 10.1128/JVI.80.7.3617-3623.2006.PubMedCentralCrossRefPubMed

22.

Friedrich TC, Valentine LE, Yant LJ, Rakasz EG, Piaskowski SM, Furlott JR, Weisgrau KL, Burwitz B, May GE, Leon EJ, Soma T, Napoe G, Capuano SV, Wilson NA, Watkins DI: Subdominant CD8+ T-cell responses are involved in durable control of AIDS virus replication. J Virol. 2007, 81 (7): 3465-3476. 10.1128/JVI.02392-06.PubMedCentralCrossRefPubMed

23.

Bennett MS, Joseph A, Ng HL, Goldstein H, Yang OO: Fine-tuning of T-cell receptor avidity to increase HIV epitope variant recognition by cytotoxic T lymphocytes. Aids. 2010

24.

Chen H, Piechocka-Trocha A, Miura T, Brockman MA, Julg BD, Baker BM, Rothchild AC, Block BL, Schneidewind A, Koibuchi T, Pereyra F, Allen TM, Walker BD: Differential neutralization of human immunodeficiency virus (HIV) replication in autologous CD4 T cells by HIV-specific cytotoxic T lymphocytes. J Virol. 2009, 83 (7): 3138-3149. 10.1128/JVI.02073-08.PubMedCentralCrossRefPubMed

25.

Almeida JR, Price DA, Papagno L, Arkoub ZA, Sauce D, Bornstein E, Asher TE, Samri A, Schnuriger A, Theodorou I, Costagliola D, Rouzioux C, Agut H, Marcelin AG, Douek D, Autran B, Appay V: Superior control of HIV-1 replication by CD8+ T cells is reflected by their avidity, polyfunctionality, and clonal turnover. J Exp Med. 2007, 204 (10): 2473-2485. 10.1084/jem.20070784.PubMedCentralCrossRefPubMed

26.

Almeida JR, Sauce D, Price DA, Papagno L, Shin SY, Moris A, Larsen M, Pancino G, Douek DC, Autran B, Saez-Cirion A, Appay V: Antigen sensitivity is a major determinant of CD8+ T-cell polyfunctionality and HIV-suppressive activity. Blood. 2009, 113 (25): 6351-6360. 10.1182/blood-2009-02-206557.PubMedCentralCrossRefPubMed

27.

Saez-Cirion A, Lacabaratz C, Lambotte O, Versmisse P, Urrutia A, Boufassa F, Barre-Sinoussi F, Delfraissy JF, Sinet M, Pancino G, Venet A: HIV controllers exhibit potent CD8 T cell capacity to suppress HIV infection ex vivo and peculiar cytotoxic T lymphocyte activation phenotype. Proc Natl Acad Sci USA. 2007, 104 (16): 6776-6781. 10.1073/pnas.0611244104.PubMedCentralCrossRefPubMed

28.

Julg B, Williams KL, Reddy S, Bishop K, Qi Y, Carrington M, Goulder PJ, Ndung'u T, Walker BD: Enhanced anti-HIV functional activity associated with Gag-specific CD8 T-cell responses. J Virol. 2010, 84 (11): 5540-5549. 10.1128/JVI.02031-09.PubMedCentralCrossRefPubMed

29.

Berger C, Frahm N, Price D, Mothe B, Ghebremichael M, Hartman K, Henry L, Brenchley J, Ruff L, Venturi V, Pereyra F, Sidney J, Sette A, Douek D, Walker B, Kaufmann D, Brander C: High functional avidity CTL responses to HLA-B-restricted Gag-derived epitopes associate with relative HIV control. J Virology. 2011, 85 (18): 9334-9345.PubMedCentralCrossRefPubMed

30.

Bunce M, O'Neill CM, Barnardo MC, Krausa P, Browning MJ, Morris PJ, Welsh KI: Phototyping: comprehensive DNA typing for HLA-A, B, C, DRB1, DRB3, DRB4, DRB5 & DQB1 by PCR with 144 primer mixes utilizing sequence- specific primers (PCR-SSP). Tissue Antigens. 1995, 46 (5): 355-367. 10.1111/j.1399-0039.1995.tb03127.x.CrossRefPubMed

31.

Frahm N, Korber BT, Adams CM, Szinger JJ, Draenert R, Addo MM, Feeney ME, Yusim K, Sango K, Brown NV, SenGupta D, Piechocka-Trocha A, Simonis T, Marincola FM, Wurcel AG, Stone DR, Russell CJ, Adolf P, Cohen D, Roach T, StJohn A, Khatri A, Davis K, Mullins J, Goulder PJ, Walker BD, Brander C: Consistent cytotoxic-T-lymphocyte targeting of immunodominant regions in human immunodeficiency virus across multiple ethnicities. J Virol. 2004, 78 (5): 2187-2200. 10.1128/JVI.78.5.2187-2200.2004.PubMedCentralCrossRefPubMed

32.

Frahm N, Nickle DC, Linde CH, Cohen DE, Zuniga R, Lucchetti A, Roach T, Walker BD, Allen TM, Korber BT, Mullins JI, Brander C: Increased detection of HIV-specific T cell responses by combination of central sequences with comparable immunogenicity. Aids. 2008, 22 (4): 447-456. 10.1097/QAD.0b013e3282f42412.CrossRefPubMed

33.

Kiepiela P, Leslie AJ, Honeyborne I, Ramduth D, Thobakgale C, Chetty S, Rathnavalu P, Moore C, Pfafferott KJ, Hilton L, Zimbwa P, Moore S, Allen T, Brander C, Addo MM, Altfeld M, James I, Mallal S, Bunce M, Barber LD, Szinger J, Day C, Klenerman P, Mullins J, Korber B, Coovadia HM, Walker BD, Goulder PJ: Coevolutionary influences of HIV and HLA: the dominant role of HLA-B. Nature. 2004, 432: 769-774. 10.1038/nature03113.CrossRefPubMed

34.

Andre P, Groettrup M, Klenerman P, de Giuli R, Booth BL, Cerundolo V, Bonneville M, Jotereau F, Zinkernagel RM, Lotteau V: An inhibitor of HIV-1 protease modulates proteasome activity, antigen presentation, and T cell responses. Proc Natl Acad Sci. 1998, 95 (22): 13120-13124. 10.1073/pnas.95.22.13120.PubMedCentralCrossRefPubMed

35.

Ali A, Jamieson BD, Yang OO: Half-genome human immunodeficiency virus type 1 constructs for rapid production of reporter viruses. J Virol Methods. 2003, 110 (2): 137-142. 10.1016/S0166-0934(03)00110-1.CrossRefPubMed

36.

Hu Z, Kuritzkes DR: Effect of raltegravir resistance mutations in HIV-1 integrase on viral fitness. J Acquir Immune Defic Syndr. 2010, 55 (2): 148-155. 10.1097/QAI.0b013e3181e9a87a.PubMedCentralCrossRefPubMed

37.

Adnan S, Balamurugan A, Trocha A, Bennett MS, Ng HL, Ali A, Brander C, Yang OO: Nef interference with HIV-1-specific CTL antiviral activity is epitope specific. Blood. 2006, 108 (10): 3414-3419. 10.1182/blood-2006-06-030668.PubMedCentralCrossRefPubMed

38.

Gibbs JS, Regier DA, Desrosiers RC: Construction and in vitro properties of HIV-1 mutants with deletions in "nonessential" genes. AIDS Res Hum Retroviruses. 1994, 10 (4): 343-350. 10.1089/aid.1994.10.343.CrossRefPubMed

39.

Berger CT, Carlson JM, Brumme CJ, Hartman KL, Brumme ZL, Henry LM, Rosato PC, Piechocka-Trocha A, Brockman MA, Harrigan PR, Heckerman D, Kaufmann DE, Brander C: Viral adaptation to immune selection pressure by HLA class I-restricted CTL responses targeting epitopes in HIV frameshift sequences. J Exp Med. 2010, 207 (1): 61-75. 10.1084/jem.20091808.PubMedCentralCrossRefPubMed

40.

Team RDC: R: A Language and Environment for Statistical Computing. 2010, R Foundation for Statistical Computing, [http://www.R-project.org]

41.

Liebminger A, Seyfang L, Filzmoser P, Varmuza K: A New Variable Selection Method Based on All Subsets Regression. 10th SSC 2007, Scandinavian Symposium on Chemometrics:. 2007

42.

Seyfang L: Heuristiken zur Variablenselektion bei hochdimensionalen Daten. Institut für Statistik und Wahrscheinlichkeitstheorie, Technische Universität Wien, Vienna. 2008

43.

Pérez-Álvarez S, Gomez G, Pérez-Álvarez N, Brander C: Technical Report: Use of comprehensive cohort data to identify host genetic and immunological and virological factors associated with relative in vivo control of HIV. Deparment of Statistics and Operational Research, Universitat Politècnica de Catalunya (UPC), Barcelona. 2011

44.

Llano A, Frahm N, Brander C: How to Optimally Define Optimal Cytotoxic T Lymphocyte Epitopes in HIV Infection?. HIV Molecular immunology database. Edited by: Korber CB B, Walker B, Koup R, Moore J, Haynes B, Meyers G. 2009, Los Alamos, NM, USA: Los Alamos National Laboratory: Theoretical Biology and Biophysics

45.

Goulder PJ, Brander C, Annamalai K, Mngqundaniso N, Govender U, Tang Y, He S, Hartman KE, O'Callaghan CA, Ogg GS, Altfeld MA, Rosenberg ES, Cao H, Kalams SA, Hammond M, Bunce M, Pelton SI, Burchett SA, McIntosh K, Coovadia HM, Walker BD: Differential narrow focusing of immunodominant human immunodeficiency virus gag-specific cytotoxic T-lymphocyte responses in infected african and caucasoid adults and children. J Virol. 2000, 74 (12): 5679-5690. 10.1128/JVI.74.12.5679-5690.2000.PubMedCentralCrossRefPubMed

46.

Kawashima Y, Pfafferott K, Frater J, Matthews P, Payne R, Addo M, Gatanaga H, Fujiwara M, Hachiya A, Koizumi H, Kuse N, Oka S, Duda A, Prendergast A, Crawford H, Leslie A, Brumme Z, Brumme C, Allen T, Brander C, Kaslow R, Tang J, Hunter E, Allen S, Mulenga J, Branch S, Roach T, John M, Mallal S, Ogwu A: Adaptation of HIV-1 to human leukocyte antigen class I. Nature. 2009, 458 (7238): 641-645. 10.1038/nature07746.PubMedCentralCrossRefPubMed

47.

Leslie A, Matthews PC, Listgarten J, Carlson JM, Kadie C, Ndung'u T, Brander C, Coovadia H, Walker BD, Heckerman D, Goulder PJ: Additive contribution of HLA class I alleles in the immune control of HIV-1 infection. J Virol. 2010, 84 (19): 9879-9888. 10.1128/JVI.00320-10.PubMedCentralCrossRefPubMed

48.

Yang OO, Kalams SA, Trocha A, Cao H, Luster A, Johnson RP, Walker BD: Suppression of human immunodeficiency virus type 1 replication by CD8+ cells: evidence for HLA class 1-restricted triggering of cytolytic and noncytolytic mechanisms. J Virol. 1997, 71 (4): 3120-3128.PubMedCentralPubMed

49.

Rolland M, Heckerman D, Deng W, Rousseau CM, Coovadia H, Bishop K, Goulder PJ, Walker BD, Brander C, Mullins JI: Broad and Gag-biased HIV-1 epitope repertoires are associated with lower viral loads. PLoS ONE. 2008, 3 (1): e1424-10.1371/journal.pone.0001424.PubMedCentralCrossRefPubMed

50.

Buchbinder SP, Mehrotra DV, Duerr A, Fitzgerald DW, Mogg R, Li D, Gilbert PB, Lama JR, Marmor M, Del Rio C, McElrath MJ, Casimiro DR, Gottesdiener KM, Chodakewitz JA, Corey L, Robertson MN: Efficacy assessment of a cell-mediated immunity HIV-1 vaccine (the Step Study): a double-blind, randomised, placebo-controlled, test-of-concept trial. Lancet. 2008, 372 (9653): 1881-1893. 10.1016/S0140-6736(08)61591-3.PubMedCentralCrossRefPubMed

51.

Rerks-Ngarm S, Pitisuttithum P, Nitayaphan S, Kaewkungwal J, Chiu J, Paris R, Premsri N, Namwat C, de Souza M, Adams E, Benenson M, Gurunathan S, Tartaglia J, McNeil JG, Francis DP, Stablein D, Birx DL, Chunsuttiwat S, Khamboonruang C, Thongcharoen P, Robb ML, Michael NL, Kunasol P, Kim JH: Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand. N Engl J Med. 2009, 361 (23): 2209-2220. 10.1056/NEJMoa0908492.CrossRefPubMed

52.

Rolland M, Nickle DC, Mullins JI: HIV-1 Group M Conserved Elements Vaccine. PLOS Pathogen. 2007, 3 (11): e157-10.1371/journal.ppat.0030157.CrossRef

53.

Addo M, Altfeld M, Rosenberg E, Eldridge B, Philips M, Habeeb K, Khatri A, Brander C, Robbins G, Mazzara G, Goulder P, Walker B: The HIV-1 regulatory proteins Tat and Rev are freqently targeted by cytotoxic T lymphocyte (CTL) derived from HIV infected individuals. Proc Nat Acad Sci. 2001, 98: 1781-1786. 10.1073/pnas.98.4.1781.PubMedCentralCrossRefPubMed

54.

Kloverpris H, Karlsson I, Bonde J, Thorn M, Vinner L, Pedersen AE, Hentze JL, Andresen BS, Svane IM, Gerstoft J, Kronborg G, Fomsgaard A: Induction of novel CD8+ T-cell responses during chronic untreated HIV-1 infection by immunization with subdominant cytotoxic T-lymphocyte epitopes. Aids. 2009, 23 (11): 1329-1340. 10.1097/QAD.0b013e32832d9b00.CrossRefPubMed

55.

Altfeld M, Allen TM: Hitting HIV where it hurts: an alternative approach to HIV vaccine design. Trends Immunol. 2006, 27 (11): 504-510. 10.1016/j.it.2006.09.007.CrossRefPubMed

56.

Frahm N, Kaufmann DE, Yusim K, Muldoon M, Kesmir C, Linde CH, Fischer W, Allen TM, Li B, McMahon BH, Faircloth KL, Hewitt HS, Mackey EW, Miura T, Khatri A, Wolinsky S, McMichael A, Funkhouser RK, Walker BD, Brander C, Korber BT: Increased sequence diversity coverage improves detection of HIV-specific T cell responses. J Immunol. 2007, 179 (10): 6638-6650.CrossRefPubMed

57.

Ibarrondo J, Zuniga R, Farfan M, Suarez J, Mothe B, Llano A, Szinger J, Hildebrand W, Sanchez J, Korber B, Brander C: Crucial contribution of sub-dominant HLA-C allele restricted CTL responses to the control of HIV. AIDs Vaccine. 2009, : 2009; Paris

58.

Frahm N, Yusim K, Adams S, Sidney J, Hraber P, Hewitt HS, Linde CH, Woodberry T, Henry L, Listgarten J, Kadie C, Jojic N, Sango K, Brown NV, Pae E, Zaman T, John M, Mallal S, Marincola F, Walker BD, Sette A, Heckerman D, Korber BT, Brander C: Extensive HLA class I allele promiscuity among viral cytotoxic T lymphocyte (CTL) epitopes. Europ J Immunol. 2007, 37: 2419-2433. 10.1002/eji.200737365.CrossRef

59.

Liu J, O'Brien KL, Lynch DM, Simmons NL, La Porte A, Riggs AM, Abbink P, Coffey RT, Grandpre LE, Seaman MS, Landucci G, Forthal DN, Montefiori DC, Carville A, Mansfield KG, Havenga MJ, Pau MG, Goudsmit J, Barouch DH: Immune control of an SIV challenge by a T-cell-based vaccine in rhesus monkeys. Nature. 2009, 457 (7225): 87-91. 10.1038/nature07469.PubMedCentralCrossRefPubMed

60.

Reece JC, Loh L, Alcantara S, Fernandez CS, Stambas J, Sexton A, De Rose R, Petravic J, Davenport MP, Kent SJ: Timing of immune escape linked to success or failure of vaccination. PLoS One. 2010, 5 (9):

61.

Letourneau S, Im EJ, Mashishi T, Brereton C, Bridgeman A, Yang H, Dorrell L, Dong T, Korber B, McMichael AJ, Hanke T: Design and pre-clinical evaluation of a universal HIV-1 vaccine. PLoS One. 2007, 2 (10): e984-10.1371/journal.pone.0000984.PubMedCentralCrossRefPubMed

62.

Koga M, Kawana-Tachikawa A, Heckerman D, Odawara T, Nakamura H, Koibuchi T, Fujii T, Miura T, Iwamoto A: Changes in impact of HLA class I allele expression on HIV-1 plasma virus loads at a population level over time. Microbiol Immunol. 2010, 54 (4): 196-205. 10.1111/j.1348-0421.2010.00206.x.CrossRefPubMed

63.

Mullins J: A global AIDS vaccine based on conserved elements of the viral proteome. AIDS Vaccine 2010: 2010; Atlanta, Georgia, USA

64.

Pereyra F, Addo MM, Kaufmann DE, Liu Y, Miura T, Rathod A, Baker B, Trocha A, Rosenberg R, Mackey E, Ueda P, Lu Z, Cohen D, Wrin T, Petropoulos CJ, Rosenberg ES, Walker BD: Genetic and immunologic heterogeneity among persons who control HIV infection in the absence of therapy. J Infect Dis. 2008, 197 (4): 563-571. 10.1086/526786.CrossRefPubMed

Title: Definition of the viral targets of protective HIV-1-specific T cell responses
Authors: Beatriz Mothe
Anuska Llano
Javier Ibarrondo
Marcus Daniels
Cristina Miranda
Jennifer Zamarreño
Vanessa Bach
Rosario Zuniga
Susana Pérez-Álvarez
Christoph T Berger
Maria C Puertas
Javier Martinez-Picado
Morgane Rolland
Marilu Farfan
James J Szinger
William H Hildebrand
Otto O Yang
Victor Sanchez-Merino
Chanson J Brumme
Zabrina L Brumme
David Heckerman
Todd M Allen
James I Mullins
Guadalupe Gómez
Philip J Goulder
Bruce D Walker
Jose M Gatell
Bonaventura Clotet
Bette T Korber
Jorge Sanchez
Christian Brander
Publication date: 01-12-2011
Publisher: BioMed Central
Published in: Journal of Translational Medicine / Issue 1/2011
Electronic ISSN: 1479-5876
DOI: https://doi.org/10.1186/1479-5876-9-208

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