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HIV T-Cell Vaccines

Part of the Advances in Experimental Medicine and Biology book series (AEMB,volume 1075)

Abstract

Some of the strongest immune correlates of controlled HIV infection include markers related to antiviral T-cell responses, especially responses mediated by CD8+ cytotoxic T lymphocytes (CTL). These observations and lessons learned from other viral infections have motivated the development of T-cell vaccine candidates to HIV in the preventive and especially in the therapeutic setting. While none of the T-cell vaccine concepts tested to date have shown sufficient efficacy, the last few years have seen some advances indicating that strategies activating the cellular adaptive immune response to HIV may present a critical component of an effective therapeutic and possibly preventive HIV vaccine. Some of the important components that a successful T-cell vaccine may need to contain and additional considerations for the design and delivery of such vaccines are discussed in this chapter.

Keywords

  • T-cell vaccine
  • HIV vaccine design

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References

  • Akahoshi T, Chikata T, Tamura Y, Gatanaga H, Oka S, Takiguchi M (2012) Selection and accumulation of an HIV-1 escape mutant by three types of HIV-1-specific cytotoxic T lymphocytes recognizing wild-type and/or escape mutant epitopes. J Virol 86(4):1971–1981. https://doi.org/10.1128/JVI.06470-11

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Alexander-Miller MA, Leggatt GR, Berzofsky JA (1996) Selective expansion of high- or low-avidity cytotoxic T lymphocytes and efficacy for adoptive immunotherapy. Proc Natl Acad Sci U S A 93(9):4102–4107

    CAS  CrossRef  Google Scholar 

  • Altfeld M, Allen TM (2006) Hitting HIV where it hurts: an alternative approach to HIV vaccine design. Trends Immunol 27(11):504–510

    CAS  CrossRef  Google Scholar 

  • Altfeld M, Addo MM, Shankarappa R, Lee PK, Allen TM, Yu XG, Rathod A, Harlow J, O’Sullivan K, Johnston MN, Goulder PJ, Mullins JI, Rosenberg ES, Brander C, Korber B, Walker BD (2003) Enhanced detection of human immunodeficiency virus type 1-specific T-cell responses to highly variable regions by using peptides based on autologous virus sequences. J Virol 77(13):7330–7340

    CAS  CrossRef  Google Scholar 

  • Baden LR, Karita E, Mutua G, Bekker LG, Gray G, Page-Shipp L, Walsh SR, Nyombayire J, Anzala O, Roux S, Laher F, Innes C, Seaman MS, Cohen YZ, Peter L, Frahm N, McElrath MJ, Hayes P, Swann E, Grunenberg N, Grazia-Pau M, Weijtens M, Sadoff J, Dally L, Lombardo A, Gilmour J, Cox J, Dolin R, Fast P, Barouch DH, Laufer DS (2016) Assessment of the safety and immunogenicity of 2 novel vaccine platforms for HIV-1 prevention: a randomized trial. Ann Intern Med 164(5):313–322. https://doi.org/10.7326/M15-0880

    CrossRef  PubMed  PubMed Central  Google Scholar 

  • Berger CT, Frahm N, Price DA, Mothe B, Ghebremichael M, Hartman KL, Henry LM, Brenchley JM, Ruff LE, Venturi V, Pereyra F, Sidney J, Sette A, Douek DC, Walker BD, Kaufmann DE, Brander C (2011) High-functional-avidity cytotoxic T lymphocyte responses to HLA-B-restricted Gag-derived epitopes associated with relative HIV control. J Virol 85(18):9334–9345. https://doi.org/10.1128/JVI.00460-11

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Bett AJ, Prevec L, Graham FL (1993) Packaging capacity and stability of human adenovirus type 5 vectors. J Virol 67(10):5911–5921

    CAS  PubMed  PubMed Central  Google Scholar 

  • Bhattacharya T, Daniels M, Heckerman D, Foley B, Frahm N, Kadie C, Carlson J, Yusim K, McMahon B, Gaschen B, Mallal S, Mullins J, Nickle D, Herbeck J, Rousseau C, Learn G, Miura T, Brander C, Walker B, Korber B (2007) Founder effects in population based assessment of HIV polymorphisms and HLA Allele Associations. Science 315:1583

    CAS  CrossRef  Google Scholar 

  • Bihl FK, Loggi E, Chisholm JV 3rd, Hewitt HS, Henry LM, Linde C, Suscovich TJ, Wong JT, Frahm N, Andreone P, Brander C (2005) Simultaneous assessment of cytotoxic T lymphocyte responses against multiple viral infections by combined usage of optimal epitope matrices, anti- CD3 mAb T-cell expansion and “RecycleSpot”. J Transl Med 3(1):20

    CrossRef  Google Scholar 

  • Billeskov R, Wang Y, Solaymani-Mohammadi S, Frey B, Kulkarni S, Andersen P, Agger EM, Sui Y, Berzofsky JA (2017) Low antigen dose in adjuvant-based vaccination selectively induces CD4 T cells with enhanced functional avidity and protective efficacy. J Immunol 198(9):3494–3506. https://doi.org/10.4049/jimmunol.1600965

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Borthwick N, Lin Z, Akahoshi T, Llano A, Silva-Arrieta S, Ahmed T, Dorrell L, Brander C, Murakoshi H, Takiguchi M, Hanke T (2017) Novel, in-natural-infection subdominant HIV-1 CD8+ T-cell epitopes revealed in human recipients of conserved-region T-cell vaccines. PLoS One 12(4):e0176418. https://doi.org/10.1371/journal.pone.0176418

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Brander C, Wyss-Coray T, Mauri D, Bettens F, Pichler WJ (1993) Carrier-mediated uptake and presentation of a major histocompatibility complex class I-restricted peptide. Eur J Immunol 23(12):3217–3223

    CAS  CrossRef  Google Scholar 

  • Brander C, Walker BD (2003) Gradual adaptation of HIV to human host populations: good or bad news? Nat Med 9(11):1359–1362 PMID: 14595431

    CAS  CrossRef  Google Scholar 

  • 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 (2008) Efficacy assessment of a cell-mediated immunity HIV-1 vaccine (the Step Study): a double-blind, randomised, placebo-controlled, test-of-concept trial. Lancet 372(9653):1881–1893

    CAS  CrossRef  Google Scholar 

  • Buggert M, Norstrom MM, Czarnecki C, Tupin E, Luo M, Gyllensten K, Sonnerborg A, Lundegaard C, Lund O, Nielsen M, Karlsson AC (2012) Characterization of HIV-specific CD4+ T cell responses against peptides selected with broad population and pathogen coverage. PLoS One 7(7):e39874. https://doi.org/10.1371/journal.pone.0039874

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Bullock TN, Mullins DW, Colella TA, Engelhard VH (2001) Manipulation of avidity to improve effectiveness of adoptively transferred CD8(+) T cells for melanoma immunotherapy in human MHC class I-transgenic mice. J Immunol 167(10):5824–5831

    CAS  CrossRef  Google Scholar 

  • Bullock TN, Mullins DW, Engelhard VH (2003) Antigen density presented by dendritic cells in vivo differentially affects the number and avidity of primary, memory, and recall CD8+ T cells. J Immunol 170(4):1822–1829

    CAS  CrossRef  Google Scholar 

  • Carlson JM, Le AQ, Shahid A, Brumme ZL (2015) HIV-1 adaptation to HLA: a window into virus-host immune interactions. Trends Microbiol 23(4):212–224. https://doi.org/10.1016/j.tim.2014.12.008

    CAS  CrossRef  PubMed  Google Scholar 

  • Chevalier MF, Julg B, Pyo A, Flanders M, Ranasinghe S, Soghoian DZ, Kwon DS, Rychert J, Lian J, Muller MI, Cutler S, McAndrew E, Jessen H, Pereyra F, Rosenberg ES, Altfeld M, Walker BD, Streeck H (2011) HIV-1-specific interleukin-21+ CD4+ T cell responses contribute to durable viral control through the modulation of HIV-specific CD8+ T cell function. J Virol 85(2):733–741. https://doi.org/10.1128/JVI.02030-10

    CAS  CrossRef  PubMed  Google Scholar 

  • Colloca S, Barnes E, Folgori A, Ammendola V, Capone S, Cirillo A, Siani L, Naddeo M, Grazioli F, Esposito ML, Ambrosio M, Sparacino A, Bartiromo M, Meola A, Smith K, Kurioka A, O’Hara GA, Ewer KJ, Anagnostou N, Bliss C, Hill AV, Traboni C, Klenerman P, Cortese R, Nicosia A (2012) Vaccine vectors derived from a large collection of simian adenoviruses induce potent cellular immunity across multiple species. Sci Transl Med 4(115):115ra112. https://doi.org/10.1126/scitranslmed.3002925

    CAS  CrossRef  Google Scholar 

  • D’Souza MP, Yang OO (2015) Adenovirus vectors as HIV-1 vaccines: where are we? What next? AIDS 29(4):395–400. https://doi.org/10.1097/QAD.0000000000000548

    CrossRef  PubMed  Google Scholar 

  • De Haan L, Hearn AR, Rivett AJ, Hirst TR (2002) Enhanced delivery of exogenous peptides into the class I antigen processing and presentation pathway. Infect Immun 70(6):3249–3258

    CrossRef  Google Scholar 

  • Deng K, Pertea M, Rongvaux A, Wang L, Durand CM, Ghiaur G, Lai J, McHugh HL, Hao H, Zhang H, Margolick JB, Gurer C, Murphy AJ, Valenzuela DM, Yancopoulos GD, Deeks SG, Strowig T, Kumar P, Siliciano JD, Salzberg SL, Flavell RA, Shan L, Siliciano RF (2015) Broad CTL response is required to clear latent HIV-1 due to dominance of escape mutations. Nature 517(7534):381–385. https://doi.org/10.1038/nature14053

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Dicks MD, Spencer AJ, Edwards NJ, Wadell G, Bojang K, Gilbert SC, Hill AV, Cottingham MG (2012) A novel chimpanzee adenovirus vector with low human seroprevalence: improved systems for vector derivation and comparative immunogenicity. PLoS One 7(7):e40385. https://doi.org/10.1371/journal.pone.0040385

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Dinter J, Duong E, Lai NY, Berberich MJ, Kourjian G, Bracho-Sanchez E, Chu D, Su H, Zhang SC, Le Gall S (2015) Variable processing and cross-presentation of HIV by dendritic cells and macrophages shapes CTL immunodominance and immune escape. PLoS Pathog 11(3):e1004725. https://doi.org/10.1371/journal.ppat.1004725

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Farris E, Brown DM, Ramer-Tait AE, Pannier AK (2016) Micro- and nanoparticulates for DNA vaccine delivery. Exp Biol Med (Maywood) 241(9):919–929. https://doi.org/10.1177/1535370216643771

    CAS  CrossRef  Google Scholar 

  • Ferre AL, Hunt PW, McConnell DH, Morris MM, Garcia JC, Pollard RB, Yee HF, Jr., Martin JN, Deeks SG, Shacklett BL (2010) HIV controllers with HLA-DRB1*13 and HLA-DQB1*06 alleles have strong, polyfunctional mucosal CD4+ T-cell responses. J Virol 84 (21):11020–11029. doi:https://doi.org/10.1128/JVI.00980-10

    CAS  CrossRef  Google Scholar 

  • 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 (2004) Consistent cytotoxic-T-lymphocyte targeting of immunodominant regions in human immunodeficiency virus across multiple ethnicities. J Virol 78(5):2187–2200

    CAS  CrossRef  Google Scholar 

  • 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 (2006) Control of human immunodeficiency virus replication by cytotoxic T lymphocytes targeting subdominant epitopes. Nat Immunol 7(2):173–178

    CAS  CrossRef  Google Scholar 

  • 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 (2007) Extensive HLA class I allele promiscuity among viral cytotoxic T lymphocyte (CTL) epitopes. Eur J Immunol 37:2419–2433

    CAS  CrossRef  Google Scholar 

  • Frater AJ, Brown H, Oxenius A, Gunthard HF, Hirschel B, Robinson N, Leslie AJ, Payne R, Crawford H, Prendergast A, Brander C, Kiepiela P, Walker BD, Goulder PJ, McLean A, Phillips RE (2007) Effective T-cell responses select human immunodeficiency virus mutants and slow disease progression. J Virol 81(12):6742–6751. https://doi.org/10.1128/JVI.00022-07

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Garcia F, Climent N, Guardo AC, Gil C, Leon A, Autran B, Lifson JD, Martinez-Picado J, Dalmau J, Clotet B, Gatell JM, Plana M, Gallart T (2013) A dendritic cell-based vaccine elicits T cell responses associated with control of HIV-1 replication. Sci Transl Med 5(166):166ra162. https://doi.org/10.1126/scitranslmed.3004682

    CAS  CrossRef  Google Scholar 

  • Garcia-Arriaza J, Perdiguero B, Heeney J, Seaman M, Montefiori DC, Labranche C, Yates NL, Shen X, Tomaras GD, Ferrari G, Foulds KE, McDermott A, Kao SF, Roederer M, Hawkins N, Self S, Yao J, Farrell P, Phogat S, Tartaglia J, Barnett SW, Burke B, Cristillo A, Weiss D, Lee C, Kibler K, Jacobs B, Asbach B, Wagner R, Ding S, Pantaleo G, Esteban M (2015) Head-to-head comparison of poxvirus NYVAC and ALVAC vectors expressing identical HIV-1 clade C immunogens in prime-boost combination with Env protein in nonhuman primates. J Virol 89(16):8525–8539. https://doi.org/10.1128/JVI.01265-15

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Gasser O, Zenhaeusern G, Honger G, Brander C, Hess C (2011) Immunosuppressive drugs asymmetrically impact circulating T cell counts and function. Scand J Immunol 73(1):76–77. https://doi.org/10.1111/j.1365-3083.2010.02472.x

    CAS  CrossRef  PubMed  Google Scholar 

  • Gil C, Climent N, Garcia F, Hurtado C, Nieto-Marquez S, Leon A, Garcia MT, Rovira C, Miralles L, Dalmau J, Pumarola T, Almela M, Martinez-Picado J, Lifson JD, Zamora L, Miro JM, Brander C, Clotet B, Gallart T, Gatell JM (2011) Ex vivo production of autologous whole inactivated HIV-1 for clinical use in therapeutic vaccines. Vaccine 29(34):5711–5724. https://doi.org/10.1016/j.vaccine.2011.05.096

    CAS  CrossRef  PubMed  Google Scholar 

  • Goletz TJ, Klimpel KR, Arora N, Leppla SH, Keith JM, Berzofsky JA (1997) Targeting HIV proteins to the major histocompatibility complex class I processing pathway with a novel gp120-anthrax toxin fusion protein. Proc Natl Acad Sci U S A 94(22):12059–12064

    CAS  CrossRef  Google Scholar 

  • Gomez CE, Najera JL, Perdiguero B, Garcia-Arriaza J, Sorzano CO, Jimenez V, Gonzalez-Sanz R, Jimenez JL, Munoz-Fernandez MA, Lopez Bernaldo de Quiros JC, Guardo AC, Garcia F, Gatell JM, Plana M, Esteban M (2011) The HIV/AIDS vaccine candidate MVA-B administered as a single immunogen in humans triggers robust, polyfunctional, and selective effector memory T cell responses to HIV-1 antigens. J Virol 85(21):11468–11478. https://doi.org/10.1128/JVI.05165-11

    CAS  CrossRef  Google Scholar 

  • Goodridge JP, Burian A, Lee N, Geraghty DE (2013) HLA-F and MHC class I open conformers are ligands for NK cell Ig-like receptors. J Immunol 191(7):3553–3562. https://doi.org/10.4049/jimmunol.1300081

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Graziani GM, Angel JB (2015) Evaluating the efficacy of therapeutic HIV vaccines through analytical treatment interruptions. J Int AIDS Soc 18:20497. https://doi.org/10.7448/IAS.18.1.20497

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Guardo AC, Joe PT, Miralles L, Bargallo ME, Mothe B, Krasniqi A, Heirman C, Garcia F, Thielemans K, Brander C, Aerts JL, Plana M (2017) Preclinical evaluation of an mRNA HIV vaccine combining rationally selected antigenic sequences and adjuvant signals (HTI-TriMix). AIDS 31(3):321–332. https://doi.org/10.1097/QAD.0000000000001276

    CAS  CrossRef  PubMed  Google Scholar 

  • Hancock G, Yang H, Yorke E, Wainwright E, Bourne V, Frisbee A, Payne TL, Berrong M, Ferrari G, Chopera D, Hanke T, Mothe B, Brander C, McElrath MJ, McMichael A, Goonetilleke N, Tomaras GD, Frahm N, Dorrell L (2015) Identification of effective subdominant anti-HIV-1 CD8+ T cells within entire post-infection and post-vaccination immune responses. PLoS Pathog 11(2):e1004658. https://doi.org/10.1371/journal.ppat.1004658

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Hansen SG, Sacha JB, Hughes CM, Ford JC, Burwitz BJ, Scholz I, Gilbride RM, Lewis MS, Gilliam AN, Ventura AB, Malouli D, Xu G, Richards R, Whizin N, Reed JS, Hammond KB, Fischer M, Turner JM, Legasse AW, Axthelm MK, Edlefsen PT, Nelson JA, Lifson JD, Fruh K, Picker LJ (2013) Cytomegalovirus vectors violate CD8+ T cell epitope recognition paradigms. Science 340(6135):1237874. https://doi.org/10.1126/science.1237874

    CAS  CrossRef  PubMed  Google Scholar 

  • Jacobson JM, Routy JP, Welles S, DeBenedette M, Tcherepanova I, Angel JB, Asmuth DM, Stein DK, Baril JG, McKellar M, Margolis DM, Trottier B, Wood K, Nicolette C (2016) Dendritic cell immunotherapy for HIV-1 infection using autologous HIV-1 RNA: a randomized, double-blind, placebo-controlled clinical trial. J Acquir Immune Defic Syndr 72(1):31–38. https://doi.org/10.1097/QAI.0000000000000926

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Karakas A, Brumme ZL, Poon AF (2015) Global database-driven assessment of HIV-1 adaptation to the immune repertoires of human populations. J Virol 89(20):10693–10695. https://doi.org/10.1128/JVI.01355-15

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Kaslow RA, Carrington M, Apple R, Park L, Munoz A, Saah AJ, Goedert JJ, Winkler C, O’Brien SJ, Rinaldo C, Detels R, Blattner W, Phair J, Erlich H, Mann DL (1996) Influence of combinations of human major histocompatibility complex genes on the course of HIV-1 infection. Nat Med 2(4):405–411

    CAS  CrossRef  Google Scholar 

  • Kaufmann DE, Bailey PM, Sidney J, Wagner B, Norris PJ, Johnston MN, Cosimi LA, Addo MM, Lichterfeld M, Altfeld M, Frahm N, Brander C, Sette A, Walker BD, Rosenberg ES (2004) Comprehensive analysis of human immunodeficiency virus type 1-specific CD4 responses reveals marked immunodominance of gag and nef and the presence of broadly recognized peptides. J Virol 78(9):4463–4477

    CAS  CrossRef  Google Scholar 

  • 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, Shapiro R, Prado JG, Fidler S, Weber J, Pybus OG, Klenerman P, Ndung’u T, Phillips R, Heckerman D, Harrigan PR, Walker BD, Takiguchi M, Goulder P (2009) Adaptation of HIV-1 to human leukocyte antigen class I. Nature 458(7238):641–645

    CAS  CrossRef  Google Scholar 

  • 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 (2007) CD8+ T-cell responses to different HIV proteins have discordant associations with viral load. Nat Med 13(1):46–53

    CAS  CrossRef  Google Scholar 

  • Kloverpris HN, Cole DK, Fuller A, Carlson J, Beck K, Schauenburg AJ, Rizkallah PJ, Buus S, Sewell AK, Goulder P (2015) A molecular switch in immunodominant HIV-1-specific CD8+ T-cell epitopes shapes differential HLA-restricted escape. Retrovirology 12:20. https://doi.org/10.1186/s12977-015-0149-5

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

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

    CAS  CrossRef  PubMed  Google Scholar 

  • Koup RA, Safrit JT, Cao Y, Andrews CA, McLeod G, Borkowsky W, Farthing C, Ho DD (1994) Temporal association of cellular immune responses with the initial control of viremia in primary human immunodeficiency virus type 1 syndrome. J Virol 68(7):4650–4655

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kovacsovics-Bankowski M, Clark K, Benacerraf B, Rock KL (1993) Efficient major histocompatibility complex class I presentation of exogenous antigen upon phagocytosis by macrophages. Proc Natl Acad Sci U S A 90(11):4942–4946

    CAS  CrossRef  Google Scholar 

  • Kulkarni V, Rosati M, Valentin A, Ganneru B, Singh A, Yan J, Rolland M, Alicea C, Beach R, Zhang G, Le Gall S, Broderick K, Sardesai N, Heckerman D, Mothe B, Brander C, Weiner D, Mullins J, Pavlakis G, Felber B (2012) Increased Breadth of the HIV-1 p24gag derived conserved element DNA vaccine compared to Immunization with p55gag DNA in Mice

    Google Scholar 

  • Laher F, Ranasinghe S, Porichis F, Mewalal N, Pretorius K, Ismail N, Buus S, Stryhn A, Carrington M, Walker BD, Ndung’u T, Ndhlovu ZM (2017) HIV controllers exhibit enhanced frequencies of major histocompatibility complex class II tetramer+ Gag-specific CD4+ T cells in chronic clade C HIV-1 infection. J Virol 91(7):e02477. https://doi.org/10.1128/JVI.02477-16

    CrossRef  PubMed  PubMed Central  Google Scholar 

  • Learmont JC, Geczy AF, Mills J, Ashton LJ, Raynes-Greenow CH, Garsia RJ, Dyer WB, McIntyre L, Oelrichs RB, Rhodes DI, Deacon NJ, Sullivan JS (1999) Immunologic and virologic status after 14 to 18 years of infection with an attenuated strain of HIV-1. A report from the Sydney Blood Bank Cohort. N Engl J Med 340(22):1715–1722. https://doi.org/10.1056/NEJM199906033402203

    CAS  CrossRef  PubMed  Google Scholar 

  • 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 (2004) HIV evolution: CTL escape mutation and reversion after transmission. Nat Med 10(3):282–289

    CAS  CrossRef  Google Scholar 

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

    CrossRef  Google Scholar 

  • Ljungberg K, Liljestrom P (2015) Self-replicating alphavirus RNA vaccines. Expert Rev Vaccines 14(2):177–194. https://doi.org/10.1586/14760584.2015.965690

    CAS  CrossRef  PubMed  Google Scholar 

  • Llano A, Olvera A, Silva-Arrieta S, Brander C (2013) Best-characterized HIV-1 CTL epitopes: the 2013 update. HIV molecular immunology 2013. Published by Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, NM. LA-UR 13-27758:3-19

    Google Scholar 

  • Lundstrom K (2016) Replicon RNA viral vectors as vaccines. Vaccines 4(4). https://doi.org/10.3390/vaccines4040039

    CrossRef  Google Scholar 

  • McMichael AJ, Koff WC (2014) Vaccines that stimulate T cell immunity to HIV-1: the next step. Nat Immunol 15(4):319–322. https://doi.org/10.1038/ni.2844

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Mothe B (2016) Shaping CTL immunodominance with conserved HIV vaccines after early treatment (BCN01). CROI 2016, poster # 320

    Google Scholar 

  • Mothe B, Ibarrondo J, Llano A, Brander C (2009) Virological, immune and host genetics markers in the control of HIV infection. Dis Markers 27(3):105–120

    CrossRef  Google Scholar 

  • Mothe B, Llano A, Ibarrondo J, Daniels M, Miranda C, Zamarreno J, Bach V, Zuniga R, Perez-Alvarez S, Berger CT, Puertas MC, Martinez-Picado J, Rolland M, Farfan M, Szinger JJ, Hildebrand WH, Yang OO, Sanchez-Merino V, Brumme CJ, Brumme ZL, Heckerman D, Allen TM, Mullins JI, Gomez G, Goulder PJ, Walker BD, Gatell JM, Clotet B, Korber BT, Sanchez J, Brander C (2011) Definition of the viral targets of protective HIV-1-specific T cell responses. J Transl Med 9(1):208. https://doi.org/10.1186/1479-5876-9-208

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Mothe B, Llano A, Ibarrondo J, Zamarreno J, Schiaulini M, Miranda C, Ruiz-Riol M, Berger CT, Herrero MJ, Palou E, Plana M, Rolland M, Khatri A, Heckerman D, Pereyra F, Walker BD, Weiner D, Paredes R, Clotet B, Felber BK, Pavlakis GN, Mullins JI, Brander C (2012) CTL responses of high functional avidity and broad variant cross-reactivity are associated with HIV control. PLoS One 7(1):e29717. https://doi.org/10.1371/journal.pone.0029717

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Mothe B, Climent N, Plana M, Rosas M, Jimenez JL, Munoz-Fernandez MA, Puertas MC, Carrillo J, Gonzalez N, Leon A, Pich J, Arnaiz JA, Gatell JM, Clotet B, Blanco J, Alcami J, Martinez-Picado J, Alvarez-Fernandez C, Sanchez-Palomino S, Guardo AC, Pena J, Benito JM, Rallon N, Gomez CE, Perdiguero B, Garcia-Arriaza J, Esteban M, Lopez Bernaldo de Quiros JC, Brander C, Garcia F (2015) Safety and immunogenicity of a modified vaccinia Ankara-based HIV-1 vaccine (MVA-B) in HIV-1-infected patients alone or in combination with a drug to reactivate latent HIV-1. J Antimicrob Chemother70(6):1833–1842. doi:https://doi.org/10.1093/jac/dkv046

  • Mothe B, Moltó J, Manzardo C, Coll J, Puertas MC, Martinez-Picado J, Hanke T, Clotet B, Brander C (2017) Viral control induced by HIVCONSV vaccines & ROMIDEPSIN in early treated individuals. CROI, LB 119

    Google Scholar 

  • Murakoshi H, Koyanagi M, Chikata T, Rahman MA, Kuse N, Sakai K, Gatanaga H, Oka S, Takiguchi M (2017) Accumulation of pol mutations selected by HLA-B*52:01-C*12:02 protective haplotype-restricted cytotoxic T lymphocytes causes low plasma viral load due to low viral fitness of mutant viruses. J Virol 91(4):e02082. https://doi.org/10.1128/JVI.02082-16

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Murray SE, Nesterenko PA, Vanarsdall AL, Munks MW, Smart SM, Veziroglu EM, Sagario LC, Lee R, Claas FHJ, Doxiadis IIN, McVoy MA, Adler SP, Hill AB (2017) Fibroblast-adapted human CMV vaccines elicit predominantly conventional CD8+ T cell responses in humans. J Exp Med 214:1889. https://doi.org/10.1084/jem.20161988

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Mutua G, Farah B, Langat R, Indangasi J, Ogola S, Onsembe B, Kopycinski JT, Hayes P, Borthwick NJ, Ashraf A, Dally L, Barin B, Tillander A, Gilmour J, De Bont J, Crook A, Hannaman D, Cox JH, Anzala O, Fast PE, Reilly M, Chinyenze K, Jaoko W, Hanke T, Hiv-Core 004 Study Group T (2016) Broad HIV-1 inhibition in vitro by vaccine-elicited CD8(+) T cells in African adults. Mol Therapy Methods Clin Develop 3:16061. https://doi.org/10.1038/mtm.2016.61

    CAS  CrossRef  Google Scholar 

  • Ondondo B, Murakoshi H, Clutton G, Abdul-Jawad S, Wee EG, Gatanaga H, Oka S, McMichael AJ, Takiguchi M, Korber B, Hanke T (2016) Novel conserved-region T-cell mosaic vaccine with high global HIV-1 coverage is recognized by protective responses in untreated infection. Mol Therapy 24(4):832–842. https://doi.org/10.1038/mt.2016.3

    CAS  CrossRef  Google Scholar 

  • Oriol-Tordera B, Llano A, Ganoza C, Cate S, Hildebrand W, Sanchez J, Calle ML, Brander C, Olvera A (2017) Impact of HLA-DRB1 allele polymorphisms on control of HIV infection 1 in a Peruvian MSM 2 cohort. HLA 90(4):234–237

    CAS  CrossRef  Google Scholar 

  • Papuchon J, Pinson P, Guidicelli GL, Bellecave P, Thomas R, LeBlanc R, Reigadas S, Taupin JL, Baril JG, Routy JP, Wainberg M, Fleury H (2014) Kinetics of HIV-1 CTL epitopes recognized by HLA I alleles in HIV-infected individuals at times near primary infection: the Provir/Latitude45 study. PLoS One 9(6):e100452. https://doi.org/10.1371/journal.pone.0100452

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Payne R, Muenchhoff M, Mann J, Roberts HE, Matthews P, Adland E, Hempenstall A, Huang KH, Brockman M, Brumme Z, Sinclair M, Miura T, Frater J, Essex M, Shapiro R, Walker BD, Ndung’u T, McLean AR, Carlson JM, Goulder PJ (2014) Impact of HLA-driven HIV adaptation on virulence in populations of high HIV seroprevalence. Proc Natl Acad Sci U S A 111(50):E5393–E5400. https://doi.org/10.1073/pnas.1413339111

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Plata F, Autran B, Martins LP, Wain HS, Raphael M, Mayaud C, Denis M, Guillon JM, Debre P (1987) AIDS virus-specific cytotoxic T lymphocytes in lung disorders. Nature 328(6128):348–351

    CAS  CrossRef  Google Scholar 

  • Ranasinghe S, Cutler S, Davis I, Lu R, Soghoian DZ, Qi Y, Sidney J, Kranias G, Flanders MD, Lindqvist M, Kuhl B, Alter G, Deeks SG, Walker BD, Gao X, Sette A, Carrington M, Streeck H (2013) Association of HLA-DRB1-restricted CD4(+) T cell responses with HIV immune control. Nat Med 19(7):930–933. https://doi.org/10.1038/nm.3229

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Rolland M, Nickle DC, Mullins JI (2007) HIV-1 Group M conserved elements vaccine. PLoS Pathog 3(11):e157

    CrossRef  Google Scholar 

  • Rolland M, Edlefsen PT, Larsen BB, Tovanabutra S, Sanders-Buell E, Hertz T, deCamp AC, Carrico C, Menis S, Magaret CA, Ahmed H, Juraska M, Chen L, Konopa P, Nariya S, Stoddard JN, Wong K, Zhao H, Deng W, Maust BS, Bose M, Howell S, Bates A, Lazzaro M, O’Sullivan A, Lei E, Bradfield A, Ibitamuno G, Assawadarachai V, O’Connell RJ, deSouza MS, Nitayaphan S, Rerks-Ngarm S, Robb ML, McLellan JS, Georgiev I, Kwong PD, Carlson JM, Michael NL, Schief WR, Gilbert PB, Mullins JI, Kim JH (2012) Increased HIV-1 vaccine efficacy against viruses with genetic signatures in Env V2. Nature 490(7420):417–420. https://doi.org/10.1038/nature11519

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Roman VR, Jensen KJ, Jensen SS, Leo-Hansen C, Jespersen S, da Silva Te D, Rodrigues CM, Janitzek CM, Vinner L, Katzenstein TL, Andersen P, Kromann I, Andreasen LV, Karlsson I, Fomsgaard A (2013) Therapeutic vaccination using cationic liposome-adjuvanted HIV type 1 peptides representing HLA-supertype-restricted subdominant T cell epitopes: safety, immunogenicity, and feasibility in Guinea-Bissau. AIDS Res Hum Retrovir 29(11):1504–1512. https://doi.org/10.1089/AID.2013.0076

    CAS  CrossRef  PubMed  Google Scholar 

  • Rowland-Jones S, Sutton J, Ariyoshi K, Dong T, Gotch F, McAdam S, Whitby D, Sabally S, Gallimore A, Corrah T et al (1995) HIV-specific cytotoxic T-cells in HIV-exposed but uninfected Gambian women. Nat Med 1(1):59–64

    CrossRef  Google Scholar 

  • Ruiz-Riol M, Llano A, Ibarrondo J, Zamarreno J, Yusim K, Bach V, Mothe B, Perez-Alvarez S, Fernandez MA, Requena G, Meulbroek M, Pujol F, Leon A, Cobarsi P, Korber BT, Clotet B, Ganoza C, Sanchez J, Coll J, Brander C (2015) Alternative effector-function profiling identifies broad HIV-specific T-cell responses in highly HIV-exposed individuals who remain uninfected. J Infect Dis 211(6):936–946. https://doi.org/10.1093/infdis/jiu534

    CAS  CrossRef  PubMed  Google Scholar 

  • Sanchez-Sampedro L, Gomez CE, Mejias-Perez E, Sorzano CO, Esteban M (2012) High quality long-term CD4+ and CD8+ effector memory populations stimulated by DNA-LACK/MVA-LACK regimen in Leishmania major BALB/c model of infection. PLoS One 7(6):e38859. https://doi.org/10.1371/journal.pone.0038859

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Sanchez-Sampedro L, Gomez CE, Mejias-Perez E, Perez-Jimenez E, Oliveros JC, Esteban M (2013) Attenuated and replication-competent vaccinia virus strains M65 and M101 with distinct biology and immunogenicity as potential vaccine candidates against pathogens. J Virol 87(12):6955–6974. https://doi.org/10.1128/JVI.03013-12

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Schmitz J, Kuroda M, Santra S, Sasseville V, Simon M, Lifton M, Racz P, Tenner-Racz K, Dalesandro M, Scallon B, Ghrayeb J, Forman M, Montefiori D, Rieber E, Letvin N, Reimann K (1999) Control of viremia in simian immunodeficiency virus infection by CD8+ lymphocytes. Science 277:333–338

    Google Scholar 

  • Sei JJ, Haskett S, Kaminsky LW, Lin E, Truckenmiller ME, Bellone CJ, Buller RM, Norbury CC (2015) Peptide-MHC-I from endogenous antigen outnumber those from exogenous antigen, irrespective of APC phenotype or activation. PLoS Pathog 11(6):e1004941. https://doi.org/10.1371/journal.ppat.1004941

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Shankar P, Fabry JA, Fong DM, Lieberman J (1996) Three regions of HIV-1 gp160 contain clusters of immunodominant CTL epitopes. Immunol Lett 52:23–30

    CAS  CrossRef  Google Scholar 

  • Sidney J, Peters B, Frahm N, Brander C, Sette A (2008) HLA class I supertypes: a revised and updated classification. BMC Immunol 9:1

    CrossRef  Google Scholar 

  • Su Z, Vieweg J, Weizer AZ, Dahm P, Yancey D, Turaga V, Higgins J, Boczkowski D, Gilboa E, Dannull J (2002) Enhanced induction of telomerase-specific CD4(+) T cells using dendritic cells transfected with RNA encoding a chimeric gene product. Cancer Res 62(17):5041–5048

    CAS  PubMed  Google Scholar 

  • Swain SL, McKinstry KK, Strutt TM (2012) Expanding roles for CD4(+) T cells in immunity to viruses. Nat Rev Immunol 12(2):136–148. https://doi.org/10.1038/nri3152

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Tang J, Wilson CM, Meleth S, Myracle A, Lobashevsky E, Mulligan MJ, Douglas SD, Korber B, Vermund SH, Kaslow RA (2002) Host genetic profiles predict virological and immunological control of HIV-1 infection in adolescents. AIDS 16(17):2275–2284

    CrossRef  Google Scholar 

  • Tatsis N, Ertl HC (2004) Adenoviruses as vaccine vectors. Molecular therapy : the journal of the American Society of Gene Therapy 10(4):616–629. https://doi.org/10.1016/j.ymthe.2004.07.013

    CAS  CrossRef  Google Scholar 

  • Thompson M, Heath SL, Sweeton B, Williams K, Cunningham P, Keele BF, Sen S, Palmer BE, Chomont N, Xu Y, Basu R, Hellerstein MS, Kwa S, Robinson HL (2016) DNA/MVA vaccination of HIV-1 infected participants with viral suppression on antiretroviral therapy, followed by treatment interruption: elicitation of immune responses without control of re-emergent virus. PLoS One 11(10):e0163164. https://doi.org/10.1371/journal.pone.0163164

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Walker BD, Chakrabarti S, Moss B, Paradis TJ, Flynn T, Durno AG, Blumberg RS, Kaplan JC, Hirsch MS, Schooley RT (1987) HIV-specific cytotoxic T lymphocytes in seropositive individuals. Nature 328(6128):345–348

    CAS  CrossRef  Google Scholar 

  • Yang OO, Ali A, Kasahara N, Faure-Kumar E, Bae JY, Picker LJ, Park H (2015) Short conserved sequences of HIV-1 are highly immunogenic and shift immunodominance. J Virol 89(2):1195–1204. https://doi.org/10.1128/JVI.02370-14

    CrossRef  PubMed  Google Scholar 

  • Yerly D, Heckerman D, Allen TM, Chisholm JV, 3rd, Faircloth K, Linde CH, Frahm N, Timm J, Pichler WJ, Cerny A, Brander C (2008) Increased cytotoxic T-lymphocyte epitope variant cross-recognition and functional avidity are associated with hepatitis C virus clearance. J Virol 82 (6):3147–3153

    CAS  CrossRef  Google Scholar 

  • 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 (2006) Relative dominance of Gag p24 specific CTL is associated with HIV control. J Virol 80:3122–3125

    CrossRef  Google Scholar 

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Mothe, B., Brander, C. (2018). HIV T-Cell Vaccines. In: Zhang, L., Lewin, S. (eds) HIV Vaccines and Cure . Advances in Experimental Medicine and Biology, vol 1075. Springer, Singapore. https://doi.org/10.1007/978-981-13-0484-2_2

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