Brander C, Frahm N, Walker BD. The challenges of host and viral diversity in HIV vaccine design. Curr Opin Immunol. 2006;18:430–7.
Zuñiga R, Lucchetti A, Galvan P, Sanchez S, Sanchez C, Hernandez A, et al. Relative dominance of Gag p24-specific cytotoxic T lymphocytes is associated with human immunodeficiency virus control. J Virol. 2006;80:3122–5.
Frahm N, Kiepiela P, Adams S, Linde CH, Hewitt HS, Sango K, et al. Control of human immunodeficiency virus replication by cytotoxic T lymphocytes targeting subdominant epitopes. Nat Immunol. 2006;7:173–8.
Kiepiela P, Ngumbela K, Thobakgale C, Ramduth D, Honeyborne I, Moodley E, et al. CD8+ T-cell responses to different HIV proteins have discordant associations with viral load. Nat Med. 2007;13:46–53.
Janes H, Friedrich DP, Krambrink A, Smith RJ, Kallas EG, Horton H, et al. Vaccine-induced gag-specific T cells are associated with reduced viremia after HIV-1 infection. J Infect Dis. 2013;208:1231–9.
Ranasinghe S, Flanders M, Cutler S, Soghoian DZ, Ghebremichael M, Davis I, et al. HIV-specific CD4 T cell responses to different viral proteins have discordant associations with viral load and clinical outcome. J Virol. 2012;86:277–83.
Ranasinghe S, Cutler S, Davis I, Lu R, Soghoian DZ, Qi Y, et al. Association of HLA-DRB1-restricted CD4+ T cell responses with HIV immune control. Nat Med. 2013;19:930–3.
Sacha JB, Chung C, Rakasz EG, Spencer SP, Jonas AK, Bean AT, et al. Gag-specific CD8+ T lymphocytes recognize infected cells before AIDS-virus integration and viral protein expression. J Immunol. 2007;178:2746–54.
Chen DY, Balamurugan A, Ng HL, Cumberland WG, Yang OO. Epitope targeting and viral inoculum are determinants of Nef-mediated immune evasion of HIV-1 from cytotoxic T lymphocytes. Blood. 2012;120:100–11.
Borghans JAM, Mølgaard A, de Boer RJ, Keşmir C. HLA alleles associated with slow progression to AIDS truly prefer to present HIV-1 p24. PLoS One. 2007;2:e920.
Yang OO, Daar ES, Ng HL, Shih R, Jamieson BD. Increasing CTL targeting of conserved sequences during early HIV-1 infection is correlated to decreasing viremia. AIDS Res Hum Retroviruses. 2011;27:391–8.
Schneidewind A, Brockman MA, Yang R, Adam RI, Li B, Le Gall S, et al. 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;81:12382–93.
Brockman MA, Schneidewind A, Lahaie M, Schmidt A, Miura T, Desouza I, et al. 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;81:12608–18.
Chopera DR, Wright JK, Brockman MA, Brumme ZL. Immune-mediated attenuation of HIV-1. Future Virol. 2011;6:917–28.
Brockman MA, Brumme ZL, Brumme CJ, Miura T, Sela J, Rosato PC, et al. Early selection in Gag by protective HLA alleles contributes to reduced HIV-1 replication capacity that may be largely compensated for in chronic infection. J Virol. 2010;84:11937–49.
Troyer RM, McNevin J, Liu Y, Zhang SC, Krizan RW, Abraha A, et al. Variable fitness impact of HIV-1 escape mutations to cytotoxic T lymphocyte (CTL) response. PLoS Pathog. 2009;5:e1000365.
Kulkarni V, Rosati M, Valentin A, Ganneru B, Singh AK, Yan J, et al. HIV-1 p24(gag) derived conserved element DNA vaccine increases the breadth of immune response in mice. PLoS One. 2013;8:e60245.
Kulkarni V, Valentin A, Rosati M, Alicea C, Singh AK, Jalah R, et al. Altered response hierarchy and increased T-cell breadth upon HIV-1 conserved element DNA vaccination in Macaques. PLoS One. 2014;9:e86254.
Rolland M, Nickle DC, Mullins JI. HIV-1 group M conserved elements vaccine. PLoS Pathog. 2007;3:e157.
Dinges WL, Richardt J, Friedrich D, Jalbert E, Liu Y, Stevens CE, et al. Virus-specific CD8+ T-cell responses better define HIV disease progression than HLA genotype. J Virol. 2010;84:4461–8.
Kunwar P, Hawkins N, Dinges WL, Liu Y, Gabriel EE, Swan DA, et al. Superior control of HIV-1 replication by CD8+ T cells targeting conserved epitopes: implications for HIV vaccine design. PLoS One. 2013;8:e64405.
Niu L, Termini JM, Kanagavelu SK, Gupta S, Rolland MM, Kulkarni V, et al. Preclinical evaluation of HIV-1 therapeutic ex vivo dendritic cell vaccines expressing consensus Gag antigens and conserved Gag epitopes. Vaccine. 2011;29:2110–9.
Buchbinder SP, Mehrotra DV, Duerr A, Fitzgerald DW, Mogg R, Li D, et al. 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;372:1881–93.
Rerks-Ngarm S, Pitisuttithum P, Nitayaphan S, Kaewkungwal J, Chiu J, Paris R, et al. Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand. N Engl J Med. 2009;361:2209–20.
Hammer SM, Sobieszczyk ME, Janes H, Karuna ST, Mulligan MJ, Grove D, et al. Efficacy trial of a DNA/rAd5 HIV-1 preventive vaccine. N Engl J Med. 2013;369:2083–92.
Rolland M, Tovanabutra S, de Camp AC, Frahm N, Gilbert PB, Sanders-Buell E, et al. Genetic impact of vaccination on breakthrough HIV-1 sequences from the STEP trial. Nat Med. 2011;17:366–71.
Mothe B, Llano A, Ibarrondo J, Zamarreño J, Schiaulini M, Miranda C, et al. CTL responses of high functional avidity and broad variant cross-reactivity are associated with HIV control. PLoS One. 2012;7:e29717.
Mothe B, Llano A, Ibarrondo J, Daniels M, Miranda C, Zamarreño J, et al. Definition of the viral targets of protective HIV-1-specific T cell responses. J Transl Med. 2011;9:208.
Pollard RB, Rockstroh JK, Pantaleo G, Asmuth DM, Peters B, Lazzarin A, et al. Safety and efficacy of the peptide-based therapeutic vaccine for HIV-1, Vacc-4x: a phase 2 randomised, double-blind, placebo-controlled trial. Lancet Infect Dis. 2014;14:291–300.
Lind A, Brekke K, Sommerfelt M, Holmberg JO, Aass HCD, Baksaas I, et al. Boosters of a therapeutic HIV-1 vaccine induce divergent T cell responses related to regulatory mechanisms. Vaccine. 2013;31:4611–8.
Karlsson I, Kløverpris H, Jensen KJ, Stryhn A, Buus S, Karlsson A, et al. Identification of conserved subdominant HIV Type 1 CD8(+) T Cell epitopes restricted within common HLA Supertypes for therapeutic HIV Type 1 vaccines. AIDS Res Hum Retroviruses. 2012;28:1434–43.
Fischer W, Perkins S, Theiler J, Bhattacharya T, Yusim K, Funkhouser R, et al. Polyvalent vaccines for optimal coverage of potential T-cell epitopes in global HIV-1 variants. Nat Med. 2007;13:100–6.
Barouch DH, O’Brien KL, Simmons NL, King SL, Abbink P, Maxfield LF, et al. Mosaic HIV-1 vaccines expand the breadth and depth of cellular immune responses in rhesus monkeys. Nat Med. 2010;16:319–23.
Nickle DC, Rolland M, Jensen MA, Pond SLK, Deng W, Seligman M, et al. Coping with viral diversity in HIV vaccine design. PLoS Comput Biol. 2007;3:e75.
Fischer W, Liao HX, Haynes BF, Letvin NL, Korber B. Coping with viral diversity in HIV vaccine design: a response to Nickle et al. PLoS Comput Biol. 2008;4:e15. author reply e25.
Frahm N, Korber BT, Adams CM, Szinger JJ, Draenert R, Addo MM, et al. Consistent cytotoxic-T-lymphocyte targeting of immunodominant regions in human immunodeficiency virus across multiple ethnicities. J Virol. 2004;78:2187–200.
Nasioulas G, Zolotukhin AS, Tabernero C, Solomin L, Cunningham CP, Pavlakis GN, et al. Elements distinct from human immunodeficiency virus type 1 splice sites are responsible for the Rev dependence of env mRNA. J Virol. 1994;68:2986–93.
Schneider R, Campbell M, Nasioulas G, Felber BK, Pavlakis GN. Inactivation of the human immunodeficiency virus type 1 inhibitory elements allows Rev-independent expression of Gag and Gag/protease and particle formation. J Virol. 1997;71:4892–903.
Schwartz S, Felber BK, Pavlakis GN. Distinct RNA sequences in the gag region of human immunodeficiency virus type 1 decrease RNA stability and inhibit expression in the absence of Rev protein. J Virol. 1992;66:150–9.
Kulkarni V, Jalah R, Ganneru B, Bergamaschi C, Alicea C, von Gegerfelt A, et al. Comparison of immune responses generated by optimized DNA vaccination against SIV antigens in mice and macaques. Vaccine. 2011;29:6742–54.
Jalah R, Rosati M, Ganneru B, Pilkington GR, Valentin A, Kulkarni V, et al. The p40 subunit of interleukin (IL)-12 promotes stabilization and export of the p35 subunit: implications for improved IL-12 cytokine production. J Biol Chem. 2013;288:6763–76.
Létourneau S, Im E-J, Mashishi T, Brereton C, Bridgeman A, Yang H, et al. Design and pre-clinical evaluation of a universal HIV-1 vaccine. PLoS One. 2007;2:e984.
Nkolola JP, Wee EG-T, Im E-J, Jewell CP, Chen N, Xu X-N, et al. Engineering RENTA, a DNA prime-MVA boost HIV vaccine tailored for Eastern and Central Africa. Gene Ther. 2004;11:1068–80.
PeptGen Peptide Generator [http://www.hiv.lanl.gov/content/sequence/PEPTGEN/peptgen.html]
Patel V, Jalah R, Kulkarni V, Valentin A, Rosati M, Alicea C, et al. DNA and virus particle vaccination protects against acquisition and confers control of viremia upon heterologous simian immunodeficiency virus challenge. Proc Natl Acad Sci U S A. 2013;110:2975–80.
Burrows SR, Rossjohn J, McCluskey J. Have we cut ourselves too short in mapping CTL epitopes? Trends Immunol. 2006;27:11–6.
Le Gall S, Stamegna P, Walker BD. Portable flanking sequences modulate CTL epitope processing. J Clin Invest. 2007;117:3563–75.
Yusim K, Korber BT, Brander C, Barouch DH, de Boer RJ, Haynes BF, et al. HIV Molecular Immunology. Los Alamos, New Mex: Los Alamos Natl Lab Theor Biol Biophys; 2011.
Brumme ZL, John M, Carlson JM, Brumme CJ, Chan D, Brockman MA, et al. HLA-associated immune escape pathways in HIV-1 subtype B Gag, Pol and Nef proteins. PLoS One. 2009;4:e6687.
Liu TF, Shafer RW. Web resources for HIV type 1 genotypic-resistance test interpretation. Clin Infect Dis. 2006;42:1608–18.
Kuiken C, Foley B, Leitner T, Apetrei C, Hahn BH, Mizrachi I, et al. HIV Sequence Compendium. LA–UR: Theor Biol Biophys Group, Los Alamos Natl Lab NM; 2011. p. 11–11440.
Sidney J, Peters B, Frahm N, Brander C, Sette A. HLA class I supertypes: a revised and updated classification. BMC Immunol. 2008;9:1.
Kaufmann DE, Bailey PM, Sidney J, Wagner B, Norris PJ, Johnston MN, et al. 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. 2004;78:4463–77.
Zhang SC, Martin E, Shimada M, Godfrey SB, Fricke J, Locastro S, et al. Aminopeptidase substrate preference affects HIV epitope presentation and predicts immune escape patterns in HIV-infected individuals. J Immunol. 2012;188:5924–34.
Llano A, Williams A, Olvera A, Silvia-Arrieta S, Brander C. Best-Characterized HIV-1 CTL Epitopes: The 2013 Update. Los Alamos, New Mex: HIV Mol Immunol Los Alamos Natl Lab Theor Biol Biophys; 2013. p. 3–25.
Rihn SJ, Wilson SJ, Loman NJ, Alim M, Bakker SE, Bhella D, et al. Extreme genetic fragility of the HIV-1 capsid. PLoS Pathog. 2013;9:e1003461.
Carrington M, O’Brien SJ. The influence of HLA genotype on AIDS. Annu Rev Med. 2003;54:535–51.
O’Brien SJ, Gao X, Carrington M. HLA and AIDS: a cautionary tale. Trends Mol Med. 2001;7:379–81.
Rosati M, von Gegerfelt A, Roth P, Alicea C, Valentin A, Robert-Guroff M, et al. DNA vaccines expressing different forms of simian immunodeficiency virus antigens decrease viremia upon SIVmac251 challenge. J Virol. 2005;79:8480–92.
Dorrell L, Yang H, Ondondo B, Dong T, Gleria K, Suttill A, et al. Expansion and diversification of virus-specific T cells following immunization of Human Immunodeficiency Virus Type 1 ( HIV-1) -infected individuals with a recombinant modified vaccinia virus ankara/HIV-1 gag vaccine. J Virol. 2006;80:4705–16.
Hanke T, Goonetilleke N, McMichael AJ, Dorrell L. Clinical experience with plasmid DNA- and modified vaccinia virus Ankara-vectored human immunodeficiency virus type 1 clade A vaccine focusing on T-cell induction. J Gen Virol. 2007;88(Pt 1):1–12.
Loffredo JT, Sidney J, Bean AT, Beal DR, Bardet W, Wahl A, et al. Two MHC class I molecules associated with elite control of immunodeficiency virus replication, Mamu-B*08 and HLA-B*2705, bind peptides with sequence similarity. J Immunol. 2009;182:7763–75.
Patel V, Valentin A, Kulkarni V, Rosati M, Bergamaschi C, Jalah R, et al. Long-lasting humoral and cellular immune responses and mucosal dissemination after intramuscular DNA immunization. Vaccine. 2010;28:4827–36.
Betts MR, Nason MC, West SM, De Rosa SC, Migueles SA, Abraham J, et al. HIV nonprogressors preferentially maintain highly functional HIV-specific CD8+ T cells. Blood. 2006;107:4781–9.
Martins MA, Wilson NA, Piaskowski SM, Weisgrau KL, Furlott JR, Bonaldo MC, et al. Vaccination with gag, vif, and nef gene fragments affords partial control of viral replication after mucosal challenge with SIVmac239. J Virol. 2014;88:7493–516.
Mudd PA, Martins MA, Ericsen AJ, Tully DC, Power KA, Bean AT, et al. Vaccine-induced CD8+ T cells control AIDS virus replication. Nature. 2012;491:129–33.
Rolland M, Manocheewa S, Swain JV, Lanxon-Cookson EC, Kim M, Westfall DH, et al. HIV-1 conserved-element vaccines: relationship between sequence conservation and replicative capacity. J Virol. 2013;87:5461–7.
Manocheewa S, Swain JV, Lanxon-Cookson E, Rolland M, Mullins JI. Fitness costs of mutations at the HIV-1 capsid hexamerization interface. PLoS One. 2013;8:e66065.
Hancock G, Yang H, Yorke E, Wainwright E, Bourne V, Frisbee A, et al. Identification of effective subdominant anti-HIV-1 CD8+ T cells within entire post-infection and post-vaccination immune responses. PLoS Pathog 2015, in press.
Yang H, Wu H, Hancock G, Clutton G, Sande N, Xu X, et al. Antiviral inhibitory capacity of CD8+ T cells predicts the rate of CD4+ T-cell decline in HIV-1 infection. J Infect Dis. 2012;206:552–61.
Shan L, Deng K, Shroff NS, Durand CM, Rabi SA, Yang H-C, et al. Stimulation of HIV-1-specific cytolytic T lymphocytes facilitates elimination of latent viral reservoir after virus reactivation. Immunity. 2012;36:491–501.
Deng K, Pertea M, Rongvaux A, Wang L, Durand CM, Ghiaur G, et al. Broad CTL response is required to clear latent HIV-1 due to dominance of escape mutations. Nature. 2015;517:381–5.
Frahm N, Kaufmann DE, Yusim K, Muldoon M, Kesmir C, Linde CH, et al. Increased sequence diversity coverage improves detection of HIV-specific T cell responses. J Immunol. 2007;179:6638–50.
Rolland M, Frahm N, Nickle DC, Jojic N, Deng W, Allen TM, et al. Increased breadth and depth of cytotoxic T lymphocytes responses against HIV-1-B Nef by inclusion of epitope variant sequences. PLoS One. 2011;6:e17969.
García F, Bernaldo de Quirós JCL, Gómez CE, Perdiguero B, Nájera JL, Jiménez V, et al. Safety and immunogenicity of a modified pox vector-based HIV/AIDS vaccine candidate expressing Env, Gag, Pol and Nef proteins of HIV-1 subtype B (MVA-B) in healthy HIV-1-uninfected volunteers: A phase I clinical trial (RISVAC02). Vaccine. 2011;29:8309–16.
Chen J, Frey G, Peng H, Rits-Volloch S, Garrity J, Seaman MS, et al. Mechanism of HIV-1 neutralization by antibodies targeting a membrane-proximal region of gp41. J Virol. 2014;88:1249–58.
Hanke T, McMichael AJ. HIV-1: from escapism to conservatism. Eur J Immunol. 2011;41:3390–3.
Tubiana R, Carcelain G, Vray M, Gourlain K, Dalban C, Chermak A, et al. Therapeutic immunization with a human immunodeficiency virus (HIV) type 1-recombinant canarypox vaccine in chronically HIV-infected patients: The Vacciter Study (ANRS 094). Vaccine. 2005;23:4292–301.
Autran B, Murphy RL, Costagliola D, Tubiana R, Clotet B, Gatell J, et al. Greater viral rebound and reduced time to resume antiretroviral therapy after therapeutic immunization with the ALVAC-HIV vaccine (vCP1452). AIDS. 2008;22:1313–22.
Casazza JP, Bowman KA, Adzaku S, Smith EC, Enama ME, Bailer RT, et al. Therapeutic vaccination expands and improves the function of the HIV-specific memory T-cell repertoire. J Infect Dis. 2013;207:1829–40.
Schooley RT, Spritzler J, Wang H, Lederman MM, Havlir D, Kuritzkes DR, et al. AIDS clinical trials group 5197: a placebo-controlled trial of immunization of HIV-1-infected persons with a replication-deficient adenovirus type 5 vaccine expressing the HIV-1 core protein. J Infect Dis. 2010;202:705–16.
Hansen SG, Piatak M, Ventura AB, Hughes CM, Gilbride RM, Ford JC, et al. Immune clearance of highly pathogenic SIV infection. Nature. 2013;502:100–4.
Hansen SG, Sacha JB, Hughes CM, Ford JC, Burwitz BJ, Scholz I, et al. Cytomegalovirus vectors violate CD8+ T cell epitope recognition paradigms. Science. 2013;340:1237874.
Hansen SG, Ford JC, Lewis MS, Ventura AB, Hughes CM, Coyne-Johnson L, et al. Profound early control of highly pathogenic SIV by an effector memory T-cell vaccine. Nature. 2011;473:523–7.
Koopman G, Beenhakker N, Nieuwenhuis I, Doxiadis G, Mooij P, Drijfhout JW, et al. DNA/long peptide vaccination against conserved regions of SIV induces partial protection against SIVmac251 challenge. AIDS. 2013;27:2841–51.