Broad and Cross-Clade CD4(+) T-Cell Responses Elicited by a DNA Vaccine Encoding Highly Conserved and Promiscuous HIV-1 M-Group Consensus Peptides

Imagem de Miniatura
Arquivos
art_ALMEIDA_Broad_and_Cross_Clade_CD4(+)_T_Cell_Responses_2012.PDF (1.62 MB)
Citações na Scopus
25
Tipo de produção
article
Data de publicação
2012
Editora
PUBLIC LIBRARY SCIENCE
DOI
Indexadores
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Autores
SIDNEY, John
SETTE, Alessandro
Autor de Grupo de pesquisa
Editores
Coordenadores
Organizadores
Citação
PLOS ONE, v.7, n.9, article ID e45267, 12p, 2012
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
T-cell based vaccine approaches have emerged to counteract HIV-1/AIDS. Broad, polyfunctional and cytotoxic CD4(+) T-cell responses have been associated with control of HIV-1 replication, which supports the inclusion of CD4(+) T-cell epitopes in vaccines. A successful HIV-1 vaccine should also be designed to overcome viral genetic diversity and be able to confer immunity in a high proportion of immunized individuals from a diverse HLA-bearing population. In this study, we rationally designed a multiepitopic DNA vaccine in order to elicit broad and cross-clade CD4(+) T-cell responses against highly conserved and promiscuous peptides from the HIV-1 M-group consensus sequence. We identified 27 conserved, multiple HLA-DR-binding peptides in the HIV-1 M-group consensus sequences of Gag, Pol, Nef, Vif, Vpr, Rev and Vpu using the TEPITOPE algorithm. The peptides bound in vitro to an average of 12 out of the 17 tested HLA-DR molecules and also to several molecules such as HLA-DP, -DQ and murine IA(b) and IA(d). Sixteen out of the 27 peptides were recognized by PBMC from patients infected with different HIV-1 variants and 72% of such patients recognized at least 1 peptide. Immunization with a DNA vaccine (HIVBr27) encoding the identified peptides elicited IFN-gamma secretion against 11 out of the 27 peptides in BALB/c mice; CD4(+) and CD8(+) T-cell proliferation was observed against 8 and 6 peptides, respectively. HIVBr27 immunization elicited cross-clade T-cell responses against several HIV-1 peptide variants. Polyfunctional CD4(+) and CD8(+) T cells, able to simultaneously proliferate and produce IFN-gamma and TNF-alpha, were also observed. This vaccine concept may cope with HIV-1 genetic diversity as well as provide increased population coverage, which are desirable features for an efficacious strategy against HIV-1/AIDS.
Palavras-chave
URI
https://observatorio.fm.usp.br/handle/OPI/500
Referências
  1. Almeida JR, 2007, J EXP MED, V204, P2473, DOI 10.1084/jem.20070784
  2. Bansal A, 2006, AIDS, V20, P353, DOI 10.1097/01.aids.0000206501.16783.67
  3. Barouch DH, 2000, SCIENCE, V290, P486, DOI 10.1126/science.290.5491.486
  4. Barouch DH, 2010, NAT MED, V16, P319, DOI 10.1038/nm.2089
  5. Batista MD, 2009, PLOS ONE, P4
  6. BenMohamed L, 2003, J VIROL, V77, P9463, DOI 10.1128/JVI.77.17.9463-9473.2003
  7. Bian HJ, 2004, METHODS, V34, P468, DOI 10.1016/j.ymeth.2004.06.002
  8. Bijker MS, 2007, J IMMUNOL, V179, P5033
  9. Boaz MJ, 2002, J IMMUNOL, V169, P6376
  10. Buchbinder SP, 2008, LANCET, V372, P1881, DOI 10.1016/S0140-6736(08)61591-3
  11. Chevalier MF, 2011, J VIROL, V85, P733, DOI 10.1128/JVI.02030-10
  12. Corey L, 2009, AIDS, V23, P3, DOI 10.1097/QAD.0b013e32830e6d6d
  13. de Lalla C, 1999, J IMMUNOL, V163, P1725
  14. Depil S, 2007, J IMMUNOTHER, V30, P215, DOI 10.1097/01.cji.0000211338.99137.4f
  15. Depla E, 2008, J VIROL, V82, P435, DOI 10.1128/JVI.01505-07
  16. Douek DC, 2002, NATURE, V417, P95, DOI 10.1038/417095a
  17. Duerr A, 2012, J INFECT DIS, P206
  18. Egan MA, 2000, J VIROL, V74, P7485, DOI 10.1128/JVI.74.16.7485-7495.2000
  19. Emu B, 2005, J VIROL, V79, P14169, DOI 10.1128/JVI.79.22.14169-14178.2005
  20. Ferre AL, 2010, J VIROL, V84, P11020, DOI 10.1128/JVI.00980-10
  21. Fonseca SG, 2006, AIDS, V20, P2263, DOI 10.1097/01.aids.0000253353.48331.5f
  22. Fuller DH, 2007, VIROLOGY, V364, P245, DOI 10.1016/j.virol.2007.02.024
  23. Gaschen B, 2002, SCIENCE, V296, P2354, DOI 10.1126/science.1070441
  24. Gauduin MC, 2006, J EXP MED, V203, P2661, DOI 10.1084/jem.20060134
  25. Gloster SE, 2004, AIDS, V18, P749, DOI 10.1097/01.aids.0000111401.02002.92
  26. Hansen SG, 2011, NATURE, V473, P523, DOI 10.1038/nature10003
  27. Hansen SG, 2009, NAT MED, V15, P293, DOI 10.1038/nm.1935
  28. Haynes BF, 2012, NEW ENGLAND J MED, P366
  29. Hel Z, 2006, J IMMUNOL, V176, P85
  30. Ishioka GY, 1999, J IMMUNOL, V162, P3915
  31. Iwai LK, 2007, CLIN VACCINE IMMUNOL, V14, P474, DOI 10.1128/CVI.00458-06
  32. Iwai LK, 2003, MOL MED, V9, P209
  33. Kallas EG, 2004, BRAZ J INFECT DIS, V8, P8
  34. Kiepiela P, 2007, NAT MED, V13, P46, DOI 10.1038/nm1520
  35. Kovjazin R, 2011, VACCINE, V29, P4676, DOI 10.1016/j.vaccine.2011.04.103
  36. Lacap PA, 2008, AIDS, V22, P1029, DOI 10.1097/QAD.0b013e3282ffb3db
  37. Letourneau S, 2007, PLOS ONE, P2
  38. Liao HX, 2006, VIROLOGY, V353, P268, DOI 10.1016/j.virol.2006.04.043
  39. Liu JY, 2009, NATURE, V457, P87, DOI 10.1038/nature07469
  40. Livingston B, 2002, J IMMUNOL, V168, P5499
  41. Martins MA, 2010, J VIROL, V84, P4352, DOI 10.1128/JVI.02365-09
  42. McElrath MJ, 2010, IMMUNITY, V33, P542, DOI 10.1016/j.immuni.2010.09.011
  43. Nakanishi Y, 2009, NATURE, V462, P510, DOI 10.1038/nature08511
  44. Ngumbela KC, 2008, AIDS RES HUM RETROV, V24, P72, DOI 10.1089/aid.2007.0124
  45. Pettersen FO, 2010, CLIN EXP IMMUNOL, V161, P315, DOI 10.1111/j.1365-2249.2010.04179.x
  46. Porichis F, 2011, CURR OPIN HIV AIDS, V6, P174, DOI 10.1097/COH.0b013e3283454058
  47. Quah BJC, 2007, NAT PROTOC, V2, P2049, DOI 10.1038/nprot.2007.296
  48. Ranasinghe S, 2012, J VIROL, V86, P277, DOI 10.1128/JVI.05577-11
  49. Rerks-Ngarm S, 2009, NEW ENGL J MED, V361, P2209, DOI 10.1056/NEJMoa0908492
  50. Ribeiro SP, 2010, PLOS ONE, P5
  51. Rolland M, 2007, PLOS PATHOG, V3, P1551, DOI 10.1371/journal.ppat.0030157
  52. Rosa DS, 2006, MICROBES INFECT, V8, P2130, DOI 10.1016/j.micinf.2006.03.012
  53. Rosa DS, 2011, PLOS ONE, P6
  54. Rosenberg ES, 1997, SCIENCE, V278, P1447, DOI 10.1126/science.278.5342.1447
  55. Sacha JB, 2009, P NATL ACAD SCI USA, V106, P9791, DOI 10.1073/pnas.0813106106
  56. Sa-Filho Dercy, 2007, AIDS Res Hum Retroviruses, V23, P1087, DOI 10.1089/aid.2006.0173
  57. Samri A, 2006, CLIN VACCINE IMMUNOL, V13, P684, DOI 10.1128/CDLI.00387-05
  58. Sanabani SS, 2011, PLOS ONE, P6
  59. Santra S, 2008, P NATL ACAD SCI USA, V105, P10489, DOI 10.1073/pnas.0803352105
  60. Schroers R, 2002, CANCER RES, V62, P2600
  61. Shedlock DJ, 2003, SCIENCE, V300, P337, DOI 10.1126/science.1082305
  62. Sidney J, 2001, CURR PROTOC IMMUNOL, DOI 10.1002/0471142735.IM1803S31
  63. Staprans SI, 2004, P NATL ACAD SCI USA, V101, P13026, DOI 10.1073/pnas.0404739101
  64. Sturniolo T, 1999, NAT BIOTECHNOL, V17, P555
  65. Suhrbier Andreas, 2002, Expert Rev Vaccines, V1, P207, DOI 10.1586/14760584.1.2.207
  66. Sui YJ, 2010, P NATL ACAD SCI USA, V107, P9843, DOI 10.1073/pnas.0911932107
  67. Vaccari M, 2008, J VIROL, V82, P9629, DOI 10.1128/JVI.00893-08
  68. Weaver EA, 2006, J VIROL, V80, P6745, DOI 10.1128/JVI.02484-05
  69. Wilson CC, 2003, J IMMUNOL, V171, P5611
  70. Wilson NA, 2009, J VIROL, V83, P6508, DOI 10.1128/JVI.00272-09
  71. Zhang GL, 2005, NUCLEIC ACIDS RES, V33, pW180, DOI 10.1093/nar/gki479
  72. Zheng N, 2009, J VIROL, V83, P7668, DOI 10.1128/JVI.00513-09

Coleções
Artigos e Materiais de Revistas Científicas - FM/MCM
Artigos e Materiais de Revistas Científicas - HC/ICHC
Artigos e Materiais de Revistas Científicas - HC/InCor
Artigos e Materiais de Revistas Científicas - LIM/19
Artigos e Materiais de Revistas Científicas - LIM/60