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

Open Access 01-12-2011 | Research

Defining epitope coverage requirements for T cell-based HIV vaccines: Theoretical considerations and practical applications

Authors: Jeffrey R Currier, Merlin L Robb, Nelson L Michael, Mary A Marovich

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

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Abstract

Background

HIV vaccine development must address the genetic diversity and plasticity of the virus that permits the presentation of diverse genetic forms to the immune system and subsequent escape from immune pressure. Assessment of potential HIV strain coverage by candidate T cell-based vaccines (whether natural sequence or computationally optimized products) is now a critical component in interpreting candidate vaccine suitability.

Methods

We have utilized an N-mer identity algorithm to represent T cell epitopes and explore potential coverage of the global HIV pandemic using natural sequences derived from candidate HIV vaccines. Breadth (the number of T cell epitopes generated) and depth (the variant coverage within a T cell epitope) analyses have been incorporated into the model to explore vaccine coverage requirements in terms of the number of discrete T cell epitopes generated.

Results

We show that when multiple epitope generation by a vaccine product is considered a far more nuanced appraisal of the potential HIV strain coverage of the vaccine product emerges. By considering epitope breadth and depth several important observations were made: (1) epitope breadth requirements to reach particular levels of vaccine coverage, even for natural sequence-based vaccine products is not necessarily an intractable problem for the immune system; (2) increasing the valency (number of T cell epitope variants present) of vaccine products dramatically decreases the epitope requirements to reach particular coverage levels for any epidemic; (3) considering multiple-hit models (more than one exact epitope match with an incoming HIV strain) places a significantly higher requirement upon epitope breadth in order to reach a given level of coverage, to the point where low valency natural sequence based products would not practically be able to generate sufficient epitopes.

Conclusions

When HIV vaccine sequences are compared against datasets of potential incoming viruses important metrics such as the minimum epitope count required to reach a desired level of coverage can be easily calculated. We propose that such analyses can be applied early in the planning stages and during the execution phase of a vaccine trial to explore theoretical and empirical suitability of a vaccine product to a particular epidemic setting.
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Literature
1.
UNAIDS: AIDS: Epidemic Update: November 2009. 2009, UNAIDS/09.36E/JC1700E
2.
3.
Kim JH, Rerks-Ngarm S, Excler JL, Michael NL: HIV vaccines: lessons learned and the way forward. Curr Opin HIV AIDS. 2010, 5: 428-434. 10.1097/COH.0b013e32833d17ac.PubMedCentralCrossRefPubMed
4.
McElrath MJ, Haynes BF: Induction of immunity to human immunodeficiency virus type-1 by vaccination. Immunity. 2010, 33: 542-554. 10.1016/j.immuni.2010.09.011.PubMedCentralCrossRefPubMed
5.
Walker BD, Burton DR: Toward an AIDS vaccine. Science. 2008, 320: 760-764. 10.1126/science.1152622.CrossRefPubMed
6.
7.
Haut LH, Ertl HC: Obstacles to the successful development of an efficacious T cell-inducing HIV-1 vaccine. J Leukoc Biol. 2009, 86: 779-793. 10.1189/jlb.0209094.CrossRefPubMed
8.
Perrin H, Canderan G, Sekaly RP, Trautmann L: New approaches to design HIV-1 T-cell vaccines. Curr Opin HIV AIDS. 2010, 5: 368-376. 10.1097/COH.0b013e32833d2cc0.CrossRefPubMed
9.
Borrow P, Shattock RJ, Vyakarnam A: Innate immunity against HIV: a priority target for HIV prevention research. Retrovirology. 2010, 7: 84-10.1186/1742-4690-7-84.PubMedCentralCrossRefPubMed
10.
Palucka K, Banchereau J, Mellman I: Designing vaccines based on biology of human dendritic cell subsets. Immunity. 2010, 33: 464-478. 10.1016/j.immuni.2010.10.007.PubMedCentralCrossRefPubMed
11.
12.
13.
Virgin HW, Walker BD: Immunology and the elusive AIDS vaccine. Nature. 2010, 464: 224-231. 10.1038/nature08898.CrossRefPubMed
14.
Letvin NL, Barouch DH, Montefiori DC: Prospects for vaccine protection against HIV-1 infection and AIDS. Annu Rev Immunol. 2002, 20: 73-99. 10.1146/annurev.immunol.20.081501.094854.CrossRefPubMed
15.
16.
McMichael AJ, Borrow P, Tomaras GD, Goonetilleke N, Haynes BF: The immune response during acute HIV-1 infection: clues for vaccine development. Nat Rev Immunol. 2010, 10: 11-23. 10.1038/nri2674.PubMedCentralCrossRefPubMed
17.
Rerks-Ngarm S, Pitisuttithum P, Nitayaphan S, Kaewkungwal J, Chiu J, Paris R, Premsri N, Namwat C, de Souza M, Adams E: Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand. N Engl J Med. 2009, 361: 2209-2220. 10.1056/NEJMoa0908492.CrossRefPubMed
18.
Cresswell P, Ackerman AL, Giodini A, Peaper DR, Wearsch PA: Mechanisms of MHC class I-restricted antigen processing and cross-presentation. Immunol Rev. 2005, 207: 145-157. 10.1111/j.0105-2896.2005.00316.x.CrossRefPubMed
19.
Hansen TH, Bouvier M: MHC class I antigen presentation: learning from viral evasion strategies. Nat Rev Immunol. 2009, 9: 503-513. 10.1038/nri2575.CrossRefPubMed
20.
Loureiro J, Ploegh HL: Antigen presentation and the ubiquitin-proteasome system in host-pathogen interactions. Adv Immunol. 2006, 92: 225-305.CrossRefPubMed
21.
22.
Choudhuri K, van der Merwe PA: Molecular mechanisms involved in T cell receptor triggering. Semin Immunol. 2007, 19: 255-261. 10.1016/j.smim.2007.04.005.CrossRefPubMed
23.
Godfrey DI, Rossjohn J, McCluskey J: The fidelity, occasional promiscuity, and versatility of T cell receptor recognition. Immunity. 2008, 28: 304-314. 10.1016/j.immuni.2008.02.004.CrossRefPubMed
24.
van der Merwe PA, Dushek O: Mechanisms for T cell receptor triggering. Nat Rev Immunol. 2010, 11: 47-55.CrossRefPubMed
25.
Fischer W, Ganusov VV, Giorgi EE, Hraber PT, Keele BF, Leitner T, Han CS, Gleasner CD, Green L, Lo CC: Transmission of single HIV-1 genomes and dynamics of early immune escape revealed by ultra-deep sequencing. PLoS One. 2010, 5: e12303-10.1371/journal.pone.0012303.PubMedCentralCrossRefPubMed
26.
Korber BT, Letvin NL, Haynes BF: T-cell vaccine strategies for human immunodeficiency virus, the virus with a thousand faces. J Virol. 2009, 83: 8300-8314. 10.1128/JVI.00114-09.PubMedCentralCrossRefPubMed
27.
McCutchan FE: Understanding the genetic diversity of HIV-1. AIDS. 2000, 14 (Suppl 3): S31-44.PubMed
28.
Wood N, Bhattacharya T, Keele BF, Giorgi E, Liu M, Gaschen B, Daniels M, Ferrari G, Haynes BF, McMichael A: HIV evolution in early infection: selection pressures, patterns of insertion and deletion, and the impact of APOBEC. PLoS Pathog. 2009, 5: e1000414-10.1371/journal.ppat.1000414.PubMedCentralCrossRefPubMed
29.
De Groot AS, Marcon L, Bishop EA, Rivera D, Kutzler M, Weiner DB, Martin W: HIV vaccine development by computer assisted design: the GAIA vaccine. Vaccine. 2005, 23: 2136-2148. 10.1016/j.vaccine.2005.01.097.CrossRefPubMed
30.
Doria-Rose NA, Learn GH, Rodrigo AG, Nickle DC, Li F, Mahalanabis M, Hensel MT, McLaughlin S, Edmonson PF, Montefiori D: Human immunodeficiency virus type 1 subtype B ancestral envelope protein is functional and elicits neutralizing antibodies in rabbits similar to those elicited by a circulating subtype B envelope. J Virol. 2005, 79: 11214-11224. 10.1128/JVI.79.17.11214-11224.2005.PubMedCentralCrossRefPubMed
31.
Earl PL, Cotter C, Moss B, VanCott T, Currier J, Eller LA, McCutchan F, Birx DL, Michael NL, Marovich MA: Design and evaluation of multi-gene, multi-clade HIV-1 MVA vaccines. Vaccine. 2009, 27: 5885-5895. 10.1016/j.vaccine.2009.07.039.PubMedCentralCrossRefPubMed
32.
Fischer W, Perkins S, Theiler J, Bhattacharya T, Yusim K, Funkhouser R, Kuiken C, Haynes B, Letvin NL, Walker BD: Polyvalent vaccines for optimal coverage of potential T-cell epitopes in global HIV-1 variants. Nat Med. 2007, 13: 100-106. 10.1038/nm1461.CrossRefPubMed
33.
Gao F, Weaver EA, Lu Z, Li Y, Liao HX, Ma B, Alam SM, Scearce RM, Sutherland LL, Yu JS: Antigenicity and immunogenicity of a synthetic human immunodeficiency virus type 1 group m consensus envelope glycoprotein. J Virol. 2005, 79: 1154-1163. 10.1128/JVI.79.2.1154-1163.2005.PubMedCentralCrossRefPubMed
34.
Gaschen B, Taylor J, Yusim K, Foley B, Gao F, Lang D, Novitsky V, Haynes B, Hahn BH, Bhattacharya T, Korber B: Diversity considerations in HIV-1 vaccine selection. Science. 2002, 296: 2354-2360. 10.1126/science.1070441.CrossRefPubMed
35.
Gorse GJ, Baden LR, Wecker M, Newman MJ, Ferrari G, Weinhold KJ, Livingston BD, Villafana TL, Li H, Noonan E, Russell ND: Safety and immunogenicity of cytotoxic T-lymphocyte poly-epitope, DNA plasmid (EP HIV-1090) vaccine in healthy, human immunodeficiency virus type 1 (HIV-1)-uninfected adults. Vaccine. 2008, 26: 215-223. 10.1016/j.vaccine.2007.10.061.CrossRefPubMed
36.
Hanke T, McMichael AJ: Design and construction of an experimental HIV-1 vaccine for a year-2000 clinical trial in Kenya. Nat Med. 2000, 6: 951-955. 10.1038/79626.CrossRefPubMed
37.
Livingston BD, Newman M, Crimi C, McKinney D, Chesnut R, Sette A: Optimization of epitope processing enhances immunogenicity of multiepitope DNA vaccines. Vaccine. 2001, 19: 4652-4660. 10.1016/S0264-410X(01)00233-X.CrossRefPubMed
38.
Nickle DC, Jensen MA, Gottlieb GS, Shriner D, Learn GH, Rodrigo AG, Mullins JI: Consensus and ancestral state HIV vaccines. Science. 2003, 299: 1515-1518. author reply 1515-1518CrossRefPubMed
39.
Nickle DC, Rolland M, Jensen MA, Pond SL, Deng W, Seligman M, Heckerman D, Mullins JI, Jojic N: Coping with viral diversity in HIV vaccine design. PLoS Comput Biol. 2007, 3: e75-10.1371/journal.pcbi.0030075.PubMedCentralCrossRefPubMed
40.
41.
Thomson SA, Jaramillo AB, Shoobridge M, Dunstan KJ, Everett B, Ranasinghe C, Kent SJ, Gao K, Medveckzy J, Ffrench RA, Ramshaw IA: Development of a synthetic consensus sequence scrambled antigen HIV-1 vaccine designed for global use. Vaccine. 2005, 23: 4647-4657. 10.1016/j.vaccine.2005.04.045.CrossRefPubMed
42.
Brander C, Frahm N, Walker BD: The challenges of host and viral diversity in HIV vaccine design. Curr Opin Immunol. 2006, 18: 430-437. 10.1016/j.coi.2006.05.012.CrossRefPubMed
43.
Frahm N, Kiepiela P, Adams S, Linde CH, Hewitt HS, Sango K, Feeney ME, Addo MM, Lichterfeld M, Lahaie MP: Control of human immunodeficiency virus replication by cytotoxic T lymphocytes targeting subdominant epitopes. Nat Immunol. 2006, 7: 173-178. 10.1038/ni1281.CrossRefPubMed
44.
Frahm N, Korber BT, Adams CM, Szinger JJ, Draenert R, Addo MM, Feeney ME, Yusim K, Sango K, Brown NV: Consistent cytotoxic-T-lymphocyte targeting of immunodominant regions in human immunodeficiency virus across multiple ethnicities. J Virol. 2004, 78: 2187-2200. 10.1128/JVI.78.5.2187-2200.2004.PubMedCentralCrossRefPubMed
45.
Geldmacher C, Currier JR, Herrmann E, Haule A, Kuta E, McCutchan F, Njovu L, Geis S, Hoffmann O, Maboko L: CD8 T-cell recognition of multiple epitopes within specific Gag regions is associated with maintenance of a low steady-state viremia in human immunodeficiency virus type 1-seropositive patients. J Virol. 2007, 81: 2440-2448. 10.1128/JVI.01847-06.PubMedCentralCrossRefPubMed
46.
Goonetilleke N, Liu MK, Salazar-Gonzalez JF, Ferrari G, Giorgi E, Ganusov VV, Keele BF, Learn GH, Turnbull EL, Salazar MG: The first T cell response to transmitted/founder virus contributes to the control of acute viremia in HIV-1 infection. J Exp Med. 2009, 206: 1253-1272. 10.1084/jem.20090365.PubMedCentralCrossRefPubMed
47.
Liu Y, McNevin JP, Holte S, McElrath MJ, Mullins JI: Dynamics of viral evolution and CTL responses in HIV-1 infection. PLoS One. 2011, 6: e15639-10.1371/journal.pone.0015639.PubMedCentralCrossRefPubMed
48.
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: e1424-10.1371/journal.pone.0001424.PubMedCentralCrossRefPubMed
49.
Goepfert PA, Lumm W, Farmer P, Matthews P, Prendergast A, Carlson JM, Derdeyn CA, Tang J, Kaslow RA, Bansal A: Transmission of HIV-1 Gag immune escape mutations is associated with reduced viral load in linked recipients. J Exp Med. 2008, 205: 1009-1017. 10.1084/jem.20072457.PubMedCentralCrossRefPubMed
50.
Honeyborne I, Prendergast A, Pereyra F, Leslie A, Crawford H, Payne R, Reddy S, Bishop K, Moodley E, Nair K: Control of Hiv-1 Is Associated with Hla-B*13 and Targeting of Multiple Gag-Specific Cd8+ T Cell Epitopes. J Virol. 2007
51.
Liu J, O'Brien KL, Lynch DM, Simmons NL, La Porte A, Riggs AM, Abbink P, Coffey RT, Grandpre LE, Seaman MS: Immune control of an SIV challenge by a T-cell-based vaccine in rhesus monkeys. Nature. 2009, 457: 87-91. 10.1038/nature07469.PubMedCentralCrossRefPubMed
52.
Thurmond J, Yoon H, Kuiken C, Yusim K, Perkins S, Theiler J, Bhattacharya T, Korber B, Fischer W: Web-based design and evaluation of T-cell vaccine candidates. Bioinformatics. 2008, 24: 1639-1640. 10.1093/bioinformatics/btn251.CrossRefPubMed
53.
Currier JR, Ngauy V, de Souza MS, Ratto-Kim S, Cox JH, Polonis VR, Earl P, Moss B, Peel S, Slike B: Phase I safety and immunogenicity evaluation of MVA-CMDR, a multigenic, recombinant modified vaccinia Ankara-HIV-1 vaccine candidate. PLoS One. 2010, 5: e13983-10.1371/journal.pone.0013983.PubMedCentralCrossRefPubMed
54.
Altfeld M, Allen TM, Yu XG, Johnston MN, Agrawal D, Korber BT, Montefiori DC, O'Connor DH, Davis BT, Lee PK: HIV-1 superinfection despite broad CD8+ T-cell responses containing replication of the primary virus. Nature. 2002, 420: 434-439. 10.1038/nature01200.CrossRefPubMed
55.
Barouch DH, O'Brien KL, Simmons NL, King SL, Abbink P, Maxfield LF, Sun YH, La Porte A, Riggs AM, Lynch DM: Mosaic HIV-1 vaccines expand the breadth and depth of cellular immune responses in rhesus monkeys. Nat Med. 2010, 16: 319-323. 10.1038/nm.2089.PubMedCentralCrossRefPubMed
56.
Santra S, Liao HX, Zhang R, Muldoon M, Watson S, Fischer W, Theiler J, Szinger J, Balachandran H, Buzby A: Mosaic vaccines elicit CD8+ T lymphocyte responses that confer enhanced immune coverage of diverse HIV strains in monkeys. Nat Med. 2010, 16: 324-328. 10.1038/nm.2108.PubMedCentralCrossRefPubMed
57.
Kiepiela P, Leslie AJ, Honeyborne I, Ramduth D, Thobakgale C, Chetty S, Rathnavalu P, Moore C, Pfafferott KJ, Hilton L: Dominant influence of HLA-B in mediating the potential co-evolution of HIV and HLA. Nature. 2004, 432: 769-775. 10.1038/nature03113.CrossRefPubMed
58.
Kiepiela P, Ngumbela K, Thobakgale C, Ramduth D, Honeyborne I, Moodley E, Reddy S, de Pierres C, Mncube Z, Mkhwanazi N: CD8+ T-cell responses to different HIV proteins have discordant associations with viral load. Nat Med. 2007, 13: 46-53. 10.1038/nm1520.CrossRefPubMed
59.
Leslie A, Kavanagh D, Honeyborne I, Pfafferott K, Edwards C, Pillay T, Hilton L, Thobakgale C, Ramduth D, Draenert R: Transmission and accumulation of CTL escape variants drive negative associations between HIV polymorphisms and HLA. J Exp Med. 2005, 201: 891-902. 10.1084/jem.20041455.PubMedCentralCrossRefPubMed
60.
Leslie A, Price DA, Mkhize P, Bishop K, Rathod A, Day C, Crawford H, Honeyborne I, Asher TE, Luzzi G: 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: 4699-4708.CrossRefPubMed
61.
Leslie AJ, Pfafferott KJ, Chetty P, Draenert R, Addo MM, Feeney M, Tang Y, Holmes EC, Allen T, Prado JG: HIV evolution: CTL escape mutation and reversion after transmission. Nat Med. 2004, 10: 282-289. 10.1038/nm992.CrossRefPubMed
62.
Goulder PJ, Brander C, Tang Y, Tremblay C, Colbert RA, Addo MM, Rosenberg ES, Nguyen T, Allen R, Trocha A: Evolution and transmission of stable CTL escape mutations in HIV infection. Nature. 2001, 412: 334-338. 10.1038/35085576.CrossRefPubMed
63.
Kelleher AD, Long C, Holmes EC, Allen RL, Wilson J, Conlon C, Workman C, Shaunak S, Olson K, Goulder P: Clustered mutations in HIV-1 gag are consistently required for escape from HLA-B27-restricted cytotoxic T lymphocyte responses. J Exp Med. 2001, 193: 375-386. 10.1084/jem.193.3.375.PubMedCentralCrossRefPubMed
64.
Sandstrom E, Nilsson C, Hejdeman B, Brave A, Bratt G, Robb M, Cox J, Vancott T, Marovich M, Stout R: Broad immunogenicity of a multigene, multiclade HIV-1 DNA vaccine boosted with heterologous HIV-1 recombinant modified vaccinia virus Ankara. J Infect Dis. 2008, 198: 1482-1490. 10.1086/592507.CrossRefPubMed
65.
Catanzaro AT, Koup RA, Roederer M, Bailer RT, Enama ME, Moodie Z, Gu L, Martin JE, Novik L, Chakrabarti BK: Phase 1 safety and immunogenicity evaluation of a multiclade HIV-1 candidate vaccine delivered by a replication-defective recombinant adenovirus vector. J Infect Dis. 2006, 194: 1638-1649. 10.1086/509258.PubMedCentralCrossRefPubMed
66.
Kibuuka H, Kimutai R, Maboko L, Sawe F, Schunk MS, Kroidl A, Shaffer D, Eller LA, Kibaya R, Eller MA: A phase 1/2 study of a multiclade HIV-1 DNA plasmid prime and recombinant adenovirus serotype 5 boost vaccine in HIV-Uninfected East Africans (RV 172). J Infect Dis. 2010, 201: 600-607. 10.1086/650299.PubMedCentralCrossRefPubMed
67.
Mouquet H, Scheid JF, Zoller MJ, Krogsgaard M, Ott RG, Shukair S, Artyomov MN, Pietzsch J, Connors M, Pereyra F: Polyreactivity increases the apparent affinity of anti-HIV antibodies by heteroligation. Nature. 2010, 467: 591-595. 10.1038/nature09385.PubMedCentralCrossRefPubMed
68.
Schwickert TA, Victora GD, Fooksman DR, Kamphorst AO, Mugnier MR, Gitlin AD, Dustin ML, Nussenzweig MC: A dynamic T cell-limited checkpoint regulates affinity-dependent B cell entry into the germinal center. J Exp Med. 2011, 208: 1243-1252. 10.1084/jem.20102477.PubMedCentralCrossRefPubMed
69.
Victora GD, Schwickert TA, Fooksman DR, Kamphorst AO, Meyer-Hermann M, Dustin ML, Nussenzweig MC: Germinal center dynamics revealed by multiphoton microscopy with a photoactivatable fluorescent reporter. Cell. 2010, 143: 592-605. 10.1016/j.cell.2010.10.032.PubMedCentralCrossRefPubMed
70.
Wu X, Yang ZY, Li Y, Hogerkorp CM, Schief WR, Seaman MS, Zhou T, Schmidt SD, Wu L, Xu L: Rational design of envelope identifies broadly neutralizing human monoclonal antibodies to HIV-1. Science. 2010, 329: 856-861. 10.1126/science.1187659.PubMedCentralCrossRefPubMed
71.
Hansen SG, Ford JC, Lewis MS, Ventura AB, Hughes CM, Coyne-Johnson L, Whizin N, Oswald K, Shoemaker R, Swanson T: Profound early control of highly pathogenic SIV by an effector memory T-cell vaccine. Nature. 2011, 473: 523-527. 10.1038/nature10003.PubMedCentralCrossRefPubMed
72.
Koup RA, Roederer M, Lamoreaux L, Fischer J, Novik L, Nason MC, Larkin BD, Enama ME, Ledgerwood JE, Bailer RT: Priming immunization with DNA augments immunogenicity of recombinant adenoviral vectors for both HIV-1 specific antibody and T-cell responses. PLoS One. 2010, 5: e9015-10.1371/journal.pone.0009015.PubMedCentralCrossRefPubMed
Metadata
Title
Defining epitope coverage requirements for T cell-based HIV vaccines: Theoretical considerations and practical applications
Authors
Jeffrey R Currier
Merlin L Robb
Nelson L Michael
Mary A Marovich
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/10.1186/1479-5876-9-212

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