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. 2009 Jan 6;23:5–14. [Article in Spanish] doi: 10.1016/S0213-005X(05)75156-9

Situación actual en el desarrollo de una vacuna preventiva frente al VIH

Present situation in the development of a preventive HIV vaccine

José Alcamí a,⁎, Joan Joseph Munné b, María Ángeles Muñoz-Fernández c, Mariano Esteban d
PMCID: PMC7130300  PMID: 16373000

Abstract

El avance de la epidemia de sida ha convertido la obtención de una vacuna eficaz frente al virus de la inmunodeficiencia humana (VIH) como un objetivo científico prioritario. En el momento actual no disponemos de una vacuna preventiva frente a la infección por el VIH y en ningún modelo animal se ha conseguido la protección frente a la infección. En esta revisión se analizan las dificultades existentes en el desarrollo de una vacuna contra el sida, en especial los mecanismos de escape viral a la respuesta inmunitaria y se describen los prototipos de vacunas preventivas y terapéuticas en desarrollo y los resultados obtenidos. Por otra parte se sitúa esta investigación en el contexto sanitario, económico y social de la pandemia de sida y se analizan las polémicas actualmente planteadas en el desarrollo de ensayos clínicos con los diferentes tipos de vacunas.

Palabras clave: VIH, Sida, Vacuna, Mecanismos de escape viral, Inmunidad antiviral

Bibliografía

  • 1.WHO . WHO; Genève: 2003. UNAIDS report on the global HIV/AIDS epidemic. [Google Scholar]
  • 2.Nossal G.J.V. The global alliance for vaccines and immunization: a millennial challenge. Nature Immunol. 2000;1:1–7. doi: 10.1038/76852. [DOI] [PubMed] [Google Scholar]
  • 3.Esparza J., Bhamarapravati N. Accelerating the development and future availability of HIV-1 vaccines: why, when, where, and how? Lancet. 2000;355:2061–2066. doi: 10.1016/S0140-6736(00)02360-6. [DOI] [PubMed] [Google Scholar]
  • 4.Nabel G.J. Challenges and opportunities for development of an AIDS vaccines. Nature. 2001;410:1002–1006. doi: 10.1038/35073500. [DOI] [PubMed] [Google Scholar]
  • 5.McMichael A., Hanke T. HIV vaccines 1983-2003. Nat Med. 2003;9:874–880. doi: 10.1038/nm0703-874. [DOI] [PubMed] [Google Scholar]
  • 6.Zinkernagel R., Doherty P. MHC-restricted cytotoxic T-cells: studies on the biological role of major transplantation antigens determining T-cell restriction-specificity, function and responsiveness. Adv Immunol. 1979;27:51–177. doi: 10.1016/s0065-2776(08)60262-x. [DOI] [PubMed] [Google Scholar]
  • 7.Sung M.H., Simon R. Genomewide conserved epitope profiles of HIV-1 predicted by biophysical properties of MHC binding peptides. J Comput Biol. 2004;11:125–145. doi: 10.1089/106652704773416920. [DOI] [PubMed] [Google Scholar]
  • 8.Bandrés J.A., Zolla-Pazner S. Inmunidad humoral en la infección por el VIH. In: González J., Moreno S., Rubio R., editors. Infección por el VIH 1999. Doyma; Madrid: 1999. [Google Scholar]
  • 9.Nabel G.J., Sullivan N.J. antibodies and resistance to natural HIV infection. N Engl J Med. 2000;343:17–19. doi: 10.1056/NEJM200010263431711. [DOI] [PubMed] [Google Scholar]
  • 10.Mascola J.R., Stiegler G., VanCott T.C., Katinger H., Carpenter C.B., Hanson C.E. Protection of macaques against vaginal transmission of a pathogenic HIV-1/SIV chimeric virus by passive infusion of neutralizing antibodies. Nat Med. 2000;6:207–210. doi: 10.1038/72318. [DOI] [PubMed] [Google Scholar]
  • 11.Richman D.D., Wrin T., Little S.J., Petropoulos C.J. Rapid evolution of the neutralizing antibody response to HIV type 1 infection. Proc Natl Acad Sci U S A. 2003;100:4144–4149. doi: 10.1073/pnas.0630530100. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12.Robinson H.L., Montefiori D.C., Johnson R.P., Manson K.H., Kalish M.L., Lifson J.D. Neutralizing antibody-independent containment of immunodeficiency virus challenges by DNA priming and recombinant pox virus booster immunizations. Nat Med. 1999;5:526–534. doi: 10.1038/8406. [DOI] [PubMed] [Google Scholar]
  • 13.Moore J.P., Burton D.R. HIV-1 neutralizing antibodies: how full is the bottle? Nat Med. 1999;5:142–144. doi: 10.1038/5502. [DOI] [PubMed] [Google Scholar]
  • 14.Burton D.R. Antibodies, viruses and vaccines. Nat Rev Immunol. 2002;2:706–713. doi: 10.1038/nri891. [DOI] [PubMed] [Google Scholar]
  • 15.Burton D.R., Desrosiers R.C., Doms R.W., Koff W.C., Kwong P.D., Moore J.P. HIV vaccine design and the neutralizing antibody problem. Nat Immunol. 2004;5:233–236. doi: 10.1038/ni0304-233. [DOI] [PubMed] [Google Scholar]
  • 16.McMichael A.J., Rowland-Jones S.L. Cellular immune responses to HIV. Nature. 2001;410:980–987. doi: 10.1038/35073658. [DOI] [PubMed] [Google Scholar]
  • 17.Rosenberg E.S., Billingsley J.M., Caliendo A.M., Boswell S.L., Sax P.E., Kalams S.A. Vigorous HIV-1-specific CD4+T cell responses associated with control of viremia. Science. 1997;278:1447–1450. doi: 10.1126/science.278.5342.1447. [DOI] [PubMed] [Google Scholar]
  • 18.Ogg G.S., Jin X., Bonhoeffe S., Dunbar R.P., Nowak M.A., Monard S. Quantitation of HIV-1-specific cytotoxic T lymphocytes and plasma load of viral RNA. Science. 1998;279:2103–2106. doi: 10.1126/science.279.5359.2103. [DOI] [PubMed] [Google Scholar]
  • 19.Rosenberg E.S., Altfeld M., Poon S.H., Phillips M.N., Wilkes B.M., Eldridge R.L. Immune control of HIV-1 after early treatment of acute infection. Nature. 2000;407:523–526. doi: 10.1038/35035103. [DOI] [PubMed] [Google Scholar]
  • 20.Pitcher C.J., Quittner C., Paterson D.M., Connors M., Koup R.A., Maino V.C. HIV-1-specific CD4+ T cells are detectable in most individuals with active HIV-1 infection, but decline with prolonged viral suppression. Nature Med. 1999;5:518–525. doi: 10.1038/8400. [DOI] [PubMed] [Google Scholar]
  • 21.Richman D. The challenge of immune control of immunodeficiency virus. J Clin Invest. 1999;104:677–678. doi: 10.1172/JCI8242. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22.Metzner K.J., Jin X., Lee F.V., Gettie A., Bauer D.E., Di Mascio M. Effects of in vivo CD8+T cell depletion on virus replication in rhesus macaques immunized with a live, attenuated simian immunodeficiency virus vaccine. J Exp Med. 2000;191:1921–1931. doi: 10.1084/jem.191.11.1921. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23.Thomson M.M., Pérez-Álvarez L., Nájera R. Molecular epidemiology of HIV-1 genetic forms and its significance for vaccine development and therapy. Lancet Infect Dis. 2002;2:461–471. doi: 10.1016/s1473-3099(02)00343-2. [DOI] [PubMed] [Google Scholar]
  • 24.Letvin N.L., Walker B.D. Immunopathogenesis and immunotherapy in AIDS virus infections. Nat Med. 2003;9:861–866. doi: 10.1038/nm0703-861. [DOI] [PubMed] [Google Scholar]
  • 25.Borrow P., Lewicki H., Wei X., Horwitz M.S., Peffer N., Meyers H. Antiviral pressure exerted by HIV-1-specific cytotoxic T lymphocytes (CTLs) during primary infection demonstrated by rapid selection of CTL escape virus. Nat Med. 1997;3:205–211. doi: 10.1038/nm0297-205. [DOI] [PubMed] [Google Scholar]
  • 26.O’Connor D., Hallen T.M., Vogel T.U., Jing P., DeSouza I.P., Dodds E. Acute phase citotoxic T lymphocyte escape is a hallmarg of simian immunodeficiency virus infection. Nature Med. 2002;8:493–499. doi: 10.1038/nm0502-493. [DOI] [PubMed] [Google Scholar]
  • 27.Brander C., Hartman K.E., Trocha A.K., Jones N.G., Johnson R.P., Korber B. Lack of strong immune selection pressure by the immunodominant, HLA-A*0201-restricted cytotoxic T lymphocyte response in chronic human immunodeficiency virus-1 infection. J Clin Invest. 1998;101:2559–2566. doi: 10.1172/JCI2405. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 28.Migueles S.A., Laborico A.C., Shupert W.L., Sabbaghian M.S., Rabin R., Hallahan C.W. HIV-specific CD8+ T cell proliferation is coupled to perforin expression and is maintained in nonprogressors. Nat Immunol. 2002;3:1061–1068. doi: 10.1038/ni845. [DOI] [PubMed] [Google Scholar]
  • 29.Yang O.O. CTL ontogeny and viral escape: implications for HIV-1 vaccine design. Trends Immunol. 2004;25:138–142. doi: 10.1016/j.it.2004.01.004. [DOI] [PubMed] [Google Scholar]
  • 30.Dell H. HIV-tailored to fit. Drug Discov Today. 2004;9:101. doi: 10.1016/s1359-6446(03)02986-6. [DOI] [PubMed] [Google Scholar]
  • 31.Kwong P.D., Doyle M.L., Casper D.J., Cicala C., Leavitt S.A., Majeed S. HIV-1 evades antibody-mediated neutralization through conformational masking of receptor-binding sites. Nature. 2002;420:678–682. doi: 10.1038/nature01188. [DOI] [PubMed] [Google Scholar]
  • 32.Wei X., Decker J.M., Wang S., Hui H., Kappes J.C., Wu X. Antibody neutralization and escape by HIV-1. Nature. 2003;422:307–312. doi: 10.1038/nature01470. [DOI] [PubMed] [Google Scholar]
  • 33.Stahl-Hennig C., Steinman R.M., Tenner-Racz K., Pope M., Stolte N., Mätz-Rensing K. Rapid infection of oral mucosal-associated lymphoid tissue with simian immunodeficiency virus. Science. 1999;285:1261–1265. doi: 10.1126/science.285.5431.1261. [DOI] [PubMed] [Google Scholar]
  • 34.Haase A.T. Population biology of HIV-1 infection: viral and CD4+T cell demographics and dynamics in lymphatic tissues. Annu Rev Immunol. 1999;17:625–656. doi: 10.1146/annurev.immunol.17.1.625. [DOI] [PubMed] [Google Scholar]
  • 35.Blankson J.N., Persaud D., Siliciano R.F. The challenge of viral reservoirs in HIV-1 infection. Annu Rev Med. 2002;53:557–593. doi: 10.1146/annurev.med.53.082901.104024. [DOI] [PubMed] [Google Scholar]
  • 36.Geijtenbeek T.B., Kwon D.S., Torensma R., Van Vliet S.J., Van Duijnhoven G.C., Middel J. DC-SIGN, a dendritic cell-specific HIV-1-binding protein that enhances trans-infection of T cells. Cell. 2000;100:587–597. doi: 10.1016/s0092-8674(00)80694-7. [DOI] [PubMed] [Google Scholar]
  • 37.Douek D.C., Brenchley J.M., Betts M.R., Ambrozak D.R., Hill B.J., Okamoto Y. HIV preferentially infects HIV-specific CD4+ T cells. Nature. 2002;417:95–98. doi: 10.1038/417095a. [DOI] [PubMed] [Google Scholar]
  • 38.Daniel M.D., Kirchhoff F., Czajak S.C., Sehgal P.K., Desrosiers R.C. Protective effects of a live attenuated SIV vaccine with a deletion in the nef gene. Science. 1992;258:1938–1941. doi: 10.1126/science.1470917. [DOI] [PubMed] [Google Scholar]
  • 39.Deacon N.J., Tsykin A., Solomon A., Smith K., Ludford-Menting M., Hooker D.J. Genomic structure of an attenuated quasi species of HIV-1 from a blood transfusion donor and recipients. Science. 1995;270:988–991. doi: 10.1126/science.270.5238.988. [DOI] [PubMed] [Google Scholar]
  • 40.Baba T.W., Liska V., Khimani A.H. Live-attenuated, multiply deleted SIV causes AIDS in infants and adult macaques. Nat Med. 1995;5:194–203. doi: 10.1038/5557. [DOI] [PubMed] [Google Scholar]
  • 41.Greenough T.C., Sullivan L., Desrosiers R.C. Declining CD4 T-cell counts in a person infected with nef-deleted HIV-1. N Engl J Med. 1999;340:236–237. doi: 10.1056/NEJM199901213400314. [DOI] [PubMed] [Google Scholar]
  • 42.Sawai E.T., Hamza M.S., Ye M., Shaw K.E., Luciw P.A. Pathogenic conversion of live attenuated SIV vaccine is associated with expression of truncated. Nef J Virol. 2000;74:2038–2045. doi: 10.1128/jvi.74.4.2038-2045.2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 43.Kahn J.O., Cherng D.W., Mayer K., Murray H., Lagakos S. Evaluation of HIV-1 immunogen, an immunologic modifier, administered to patients infected whith HIV having 300 to 549 × 106/L CD4 cell counts: A randomized controlled trial. JAMA. 2000;284:2193–2202. doi: 10.1001/jama.284.17.2193. [DOI] [PubMed] [Google Scholar]
  • 44.Francis D.P., Gregory T., McElrath M.J. Advancing AIDSVAX to phase 3. Safety, immunogencity, and plans for phase 3. AIDS Res Hum Retroviruses. 1998;14:25–31. [PubMed] [Google Scholar]
  • 45.Mascola J.R., Snyder S.W., Weislow O.Sl. Immunization with envelope subunit vaccine products elicits neutralizing antibodies against laboratory-adapted but not primary isolates of human immunodeficiency virus type 1. J Infect Dis. 1996;173:34–48. doi: 10.1093/infdis/173.2.340. [DOI] [PubMed] [Google Scholar]
  • 46.Gallo R.C. Tat as one key to HIV-induced immune pathogenesis and Tat toxoid as an important component of a vaccine. Proc Natl Acad Sci U S A. 1999;96:8324–8326. doi: 10.1073/pnas.96.15.8324. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 47.Bukawa H., Sekigawa K., Hamajima K., Fujushima J., Yamada Y., Kiyono H. Neutralization of HIV-1 by secretory IgA induced by oral immunization with a new macromolecular multicomponent peptide vaccine candidate. Nature Med. 1995;1:681–685. doi: 10.1038/nm0795-681. [DOI] [PubMed] [Google Scholar]
  • 48.Seth A., Ourmanov I., Schmith J.E., Kuroda M.J., Lifton M.A., Mickerson C.E. Immunization with a modified vaccinia virus expressing simian immunodeficiency virus (SIV) Gag-Pol primes for an anamnestic Gag-specific cytotoxic T-lymphocyte response and is associated with reduction of viremia after SIV challenge. J Virol. 2000;74:2502–2509. doi: 10.1128/jvi.74.6.2502-2509.2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 49.Shiver J.W., Fu T.M., Chen L., Casimiro D.R., Davis M.E., Evans R.K. Replication-incompetent adenoviral vaccine vector elicits effective anti-immunodeficiency-virus immunity. Nature. 2002;415:331–335. doi: 10.1038/415331a. [DOI] [PubMed] [Google Scholar]
  • 50.Honda M., Matsuo K., Nakasone T., Okamoto Y., Yoshikazi H., Kitamura K. Protective immune responses induced by secretion of a chimeric soluble protein from a recombinant Mycobacterium bovis bacillus Calmette-Guérin vector candidate vaccine for human immunodeficiency virus type 1 in small animals. Proc Natl Acad Sci U S A. 1995;92:10693–10697. doi: 10.1073/pnas.92.23.10693. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 51.Trono D. Lentiviral vectors: turning a deadly foe into a therapeutic agent. Gene Ther. 2000;7:20–23. doi: 10.1038/sj.gt.3301105. [DOI] [PubMed] [Google Scholar]
  • 52.Boyer J.D., Kim J., Ugen K., Cohen A.D., Ahn L., Schuman K. HIV-1 DNA vaccines and chemokines. Vaccine. 1999;17(Suppl 2):S53–S64. doi: 10.1016/s0264-410x(99)00235-2. [DOI] [PubMed] [Google Scholar]
  • 53.Barouch D.H., Craiu A., Kuroda M.J., Schmitz J.E., Zheng X.X., Santra S. Augmentation of immune responses to HIV-1 and simian immunodeficiency virus DNA vaccines by IL-2/Ig plasmid administration in rhesus monkeys. Proc Natl Acad Sci U S A. 2000;97:4192–4197. doi: 10.1073/pnas.050417697. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 54.Gherardi M.M., Ramírez J.C., Esteban M. IL-12 and IL-18 act in synergy to clear vaccinia virus infection: involvement of innate and adaptive components of the immune system. J Gen Virol. 2003;84:1961–1972. doi: 10.1099/vir.0.19120-0. [DOI] [PubMed] [Google Scholar]
  • 55.Li S., Rodrigues M., Rodríguez D., Rodríguez J.R., Esteban M., Palese P. Priming with recombinant influenza virus followed by administration of recombinant vaccinia virus induces CD8+T-cell-mediated protective immunity against malaria. Proc Natl Acad Sci U S A. 1993;90:5214–5218. doi: 10.1073/pnas.90.11.5214. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 56.Nitayaphan S., Brown A.E. Preventive HIV vaccine development in Thailand. AIDS. 1998;S1:55–61. [PubMed] [Google Scholar]
  • 57.Ready T. AIDSVAX flop leaves vaccine field unscathed. Nat Med. 2003;9:376. doi: 10.1038/nm0403-376a. [DOI] [PubMed] [Google Scholar]
  • 58.Burton D.R., Desrosiers R.C., Doms R.W., Feinberg M.B., Gallo R.C., Hahn B. Public health. A sound rationale needed for phase III HIV-1 vaccine trials. Science. 2004;303:16. doi: 10.1126/science.1094620. [DOI] [PubMed] [Google Scholar]
  • 59.McNeil J.G., Johnston M.I., Birx D.L., Tramont E.C. Policy rebuttal. HIV vaccine trial justified. Science. 2004;303:961. doi: 10.1126/science.1096161. [DOI] [PubMed] [Google Scholar]
  • 60.Evans T.G., Keefer M.C., Weinhold K.J., Wolff M., Montefiori D., Gorse G.J. A canarypox vaccine expressing multiple human immunodeficiency virus type 1 genes given alone or with rgp120 elicits broad and durable CD8+ cytotoxic T lymphocyte responses in seronegative volunteers. J Infect Dis. 1999;180:290–298. doi: 10.1086/314895. [DOI] [PubMed] [Google Scholar]
  • 61.Hanke T., Samuel R.V., Blanchard T.J., Neumank V.C., Allen T.M., Boyson J.E. Effective induction of simian immunodeficiency virus-specific cytotoxic T lymphocytes in macaques by using a multiepitope gene and DNA primemodified vaccinia virus ankara boost vaccination regimen. J Virol. 1999;73:7524–7532. doi: 10.1128/jvi.73.9.7524-7532.1999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 62.Desrosiers R. Why an HIV vaccine is not currently within our grasp. XI CROI, San Francisco 2004 [abstract 109].
  • 63.Ferrari G., Humphrey W., McElrath M.J. Clade B-based HIV-1 vaccines elicit cross-clade cytotoxic T lymphocyte reactivities in uninfected volunteers. Proc Natl Acad Sci U S A. 1997;94:396–401. doi: 10.1073/pnas.94.4.1396. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 64.Verrier F., Burda S., Belshe R., Duliege A.M., Excler J.L., Klein M. A human immunodeficiency virus prime-boost immunization regimen in humans induces antibodies that show interclade cross-reactivity and neutralize several X4-, R5-, and dualtropic clade B and C primary isolates. J Virol. 2000;74:10025–10033. doi: 10.1128/jvi.74.21.10025-10033.2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 65.Bloom B.R. The highest attainable standard: ethical issues in AIDS vaccines. Science. 1998;279:186–188. doi: 10.1126/science.279.5348.186. [DOI] [PubMed] [Google Scholar]
  • 66.Boily M.C., Masse B.R., Desai K., Alary M., Anderson R.M. Some important issues in the planning of phase III HIV vaccine efficacy trials. Vaccine. 1999;17:989–1004. doi: 10.1016/s0264-410x(98)00316-8. [DOI] [PubMed] [Google Scholar]
  • 67.UNAIDS . WHO; Genève: 2000. Ethical considerations in HIV preventive vaccine research (document UNAIDS/00.07E. [Google Scholar]
  • 68.Klausner R.D., Fauci A.S., Corey L., Nabel G.J., Gayle H., Berkley S. The needfor a global HIV vaccine enterprise. Science. 2003;300:2036–2038. doi: 10.1126/science.1086916. [DOI] [PubMed] [Google Scholar]

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