Acquired Immunodeficiency Syndrome Vaccines: Current Concepts and Future Prospects

  • J. W. Mannhalter
Conference paper


When the National Institutes of Health (NIH) decided in 1994 that there was insufficient scientific evidence to justify progression of human immunodeficiency virus (HIV)-1 envelope-based acquired immunodeficiency syndrome (AIDS) candidate vaccines to phase III efficacy trials [1], the outlook for future AIDS vaccine research appeared to be dim. Equally low spirits could also be observed at this time in other areas of AIDS research. It has been 10 years since HIV-1 was identified as the causative agent of AIDS [2,3], yet the pathogenesis of the disease was still not fully understood and treatment of HIV infection was not available. Since then, tremendous scientific progress has been made. For example, we now know that there is no true latency in the course of HIV-1 infection; even in the so-called asymptomatic phase of the disease, large amounts of virus are produced and constantly eliminated by a potent immune system [4,5]. In addition, HIV-1 mutants with the capacity to antagonize T cell functions have been identified [6], a finding which may help to explain why the immune system eventually loses control over the HIV-1 infection. Another important observation is the resistance of CD4-positive lymphocytes to infection with HIV-1 following stimulation of these cells with anti-CD3 and anti-CD28 [7]. This was found to be due to a reduced expression or absence of chemokine receptors [8], now known to be the long-elusive HIV-1 entry cofactors [9–12]. Such HIV-1-resistant, CD4-positive lymphocytes may be important tools for both immune reconstitution and gene therapy approaches in HIV-1-infected subjects. The development of combination therapies employing inhibitors of both reverse transcriptase and HIV-1-specific protease has been one of the most important advances in AIDS research. These treatment regimens have been shown to keep the viral load in the circulation at undetectable levels for a prolonged period of time [13,14]; if these preliminary results can be confirmed in larger clinical trials, it appears that for the first time a mode of treatment, although expensive, might be available.


Human Immunodeficiency Virus Type Human Immunodeficiency Virus Infection Acquire Immune Deficiency Syndrome Simian Immunodeficiency Virus Acquire Immune Deficiency Syndrome Virus 
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  1. 1.
    Cohen J (1994) AIDS vaccine research - US panel votes to delay real-world vaccine trials. Science 264:1839PubMedGoogle Scholar
  2. 2.
    Barre-Sinoussi F, Chermann JC, Rey F, Nugeyre MT, Chamaret S, Gruest J, Dauguet C, Axler-Blin C, Vezinet-Brun F, Rouzioux C, Rozenbaum W, Montagnier L (1983) Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science 220:868–871PubMedGoogle Scholar
  3. 3.
    Popovic M, Sarngadharan MG, Read E, Gallo RC (1984) Detection, isolation and continuous production of cytopathic retroviruses (HTLV-III) from patients with AIDS and pre-AIDS. Science 224:497–500PubMedGoogle Scholar
  4. 4.
    Wei XP, Ghosh SK, Taylor ME, Johnson VA, Emini EA, Deutsch P, Lifson JD, Bonhoeffer S, Nowak MA, Hahn BH, Saag MS, Shaw GM (1995) Viral dynamics in human immunodeficiency virus type 1 infection. Nature 373:117–122PubMedGoogle Scholar
  5. 5.
    Ho DD, Neumann AU, Perelson AS, Chen W, Leonard JM, Markowitz M (1995) Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection. Nature 373:123–126PubMedGoogle Scholar
  6. 6.
    Meier UC, Klenerman P, Griffin P, James W, Koppe B, Larder B, McMichael A, Phillips R (1995) Cytotoxic T lymphocyte lysis inhibited by viable HIV mutants. Science 270:1360–1362PubMedGoogle Scholar
  7. 7.
    Levine BL, Mosca JD, Riley JL, Carroll RG, Vahey MT, Jagodzinski LL, Wagner KF, Mayers DL, Burke DS, Weislow OS, St Louis DC, June CH (1996) Antiviral effect and ex vivo CD4(+) T cell proliferation in HIV-positive patients as a result of CD28 costimulation. Science 272:1939–1943PubMedGoogle Scholar
  8. 8.
    Carroll RG, Riley JL, Levine BL, Feng Y, Kaushal S, Ritchey DW, Bernstein W, Weislow OS, Brown CR, Berger EA, June CH, St. Louis DC (1997) Differential regulation of HIV-1 fusion cofactor expression by CD28 costimulation of CD4 + T cells. Science 276:273PubMedGoogle Scholar
  9. 9.
    Choe H, Farzan M, Sun Y, Sullivan N, Rollins B, Ponath PD, Wu LJ, Maay CR, Larosa G, Newman W, Gerard N, Gerard C, Sodroski J (1996) The beta-chemokine receptors CCR3 and CCR5 facilitate infection by primary HIV-1 isolates. Cell 85:1135–1148PubMedGoogle Scholar
  10. 10.
    Deng HK, Liu R, Ellmeier W, Choe S, Unutmaz D, Burkhart M, Dimarzio P, Marmon S, Sutton RE, Hill CM, Davis CB, Peiper SC, Schall TJ, Littman DR, Landau NR (1996) Identification of a major co-receptor for primary isolates of HIV-1. Nature 381:661–666PubMedGoogle Scholar
  11. 11.
    Dragic T, Litwin V, Allaway GP, Martin SR, Huang YX, Nagashima KA, Cayanan C, Maddon PJ, Koup RA, Moore JP, Paxton WA (1996) HIV-1 entry into CD4 (-I-) cells is mediated by the chemokine receptor CC-CKR-5. Nature 381:667–673PubMedGoogle Scholar
  12. 12.
    Feng Y, Broder CC, Kennedy PE, Berger EA (1996) HIV-1 entry cofactor: functional NA cloning of a seven-transmembrane, G protein-coupled receptor. Science 272:872–877PubMedGoogle Scholar
  13. 13.
    Perelson AS, Essunger P, Cao Y, Vesanen M, Hurley A, Saksela K, Markowitz M, Ho DD (1997) Decay characteristics of HIV-1-infected compartments during combination therapy. Nature 387:188–191PubMedGoogle Scholar
  14. 14.
    Luzuriaga K, Bryson Y, Krogstad P, Robinson J, Stechenberg B, Lamson M, Cort S, Sullivan JL (1997) Combination treatment with zidovudine, didanosine and nevirapine in infants with human immunodeficiency virus type 1 infection. N Engl J Med 336:1343–1349PubMedGoogle Scholar
  15. 15.
    Desrosiers RC (1995) Non-human primate models for AIDS vaccines. AIDS 9 [Suppl A]:S137-S141PubMedGoogle Scholar
  16. 16.
    Goldstein G (1996) HIV-1 Tat protein as a potential AIDS vaccine. Nature Med 2:960–964PubMedGoogle Scholar
  17. 17.
    Montagnier L (1995) Nef vaccination against HIV disease. Lancet 346:1170PubMedGoogle Scholar
  18. 18.
    Berman PW, Gregory TJ, Riddle L, Nakamura GR, Champe MA, Porter JP, Wurm FM, Hershberg RD, Cobb EK, Eichberg JW (1990) Protection of chimpanzees from infection by HIV-1 after vaccination with recombinant glycoprotein gp120 but not gp160. Nature 345:622–625PubMedGoogle Scholar
  19. 19.
    Girard M, Kieny M.-P, Pinter A, Barre-Sinoussi F, Nara P, Kolbe H, Kusumi K, Chaput A, Reinhart T, Muchmore E, Ronco J, Kaczorek M, Gomard E, Gluckman J-C, Fultz PN (1991) Immunization of chimpanzees confers protection against challenge with human immunodeficiency virus. Proc Natl Acad Sci USA 88:542–546PubMedGoogle Scholar
  20. 20.
    Bruck C, Thiriart C, Fabry L, Francotte M, Pala P, Vanopstal O, Culp J, Rosenberg M, Dewilde M, Heidt P, Heeney J (1994) HIV-1 envelope-elicited neutralizing antibody titres correlate with protection and virus load in chimpanzees. Vaccine 12:1141–1148PubMedGoogle Scholar
  21. 21.
    Barrett N, Eder G, Dorner F (1991) Characterization of a vaccinia-derived recombinant HIV-1 gp160 candidate vaccine and its immunogenicity in chimpanzees. Biol Ther 2:91–106Google Scholar
  22. 22.
    Berman PW, Murthy KK, Wrin T, Vennari JC, Cobb EK, Eastman DJ, Champe M, Nakamura GR, Davison D, Powell MF, Bussiere J, Francis DP, Matthews T, Gregory TJ, Obijeski JF (1996) Protection of MN-rgp120-immunized chimpanzees from heterologous infection with a primary isolate of human immunodeficiency virus type 1. J Infect Dis 173:52–59PubMedGoogle Scholar
  23. 23.
    Girard M, Yue L, Barre-Sinoussi F, van der Ryst E, Meignier B, Muchmore E, Fultz PN (1996) Failure of a human immunodeficiency virus type 1 (HIV-1) subtype B-derived vaccine to prevent infection of chimpanzees by an HIV-1 subtype E strain. J Virol 70:8229–8233Google Scholar
  24. 24.
    Heeney JL (1995) AIDS: a disease of impaired Th-cell renewal. Immunol Today 16:515–520PubMedGoogle Scholar
  25. 25.
    Dolin R (1995) Human studies in the development of human immunodeficiency virus vaccines. J Infect Dis 172:1175–1183PubMedGoogle Scholar
  26. 26.
    Mascola JR, Snyder SW, Weislow OS, Belay SM, Belshe RB, Schwartz DH, Clements ML, Dolin R, Graham BS, Gorse GJ, Keefer MC, McElrath MJ, Walker MC, Wagner KF, McNeil JG, McCutchan FE, Burke DS (1996) 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 173:340–348PubMedGoogle Scholar
  27. 27.
    Salmon-Ceron D, Excler JL, Sicard D, Blanche P, Finkielstzjen L, Gluckman JC, Autran B, Matthews TJ, Meignier B, Kieny MP, Valentin C, Gönnet P, Diaz I, Salomon H, Pialoux G, Gonzalez-Canali G, Plotkin S (1995) Safety and immunogenicity of a recombinant HIV type 1 glycoprotein 160 boosted by a V3 synthetic peptide in HIV-negative volunteers. AIDS Res Hum Retroviruses 11:1479–1486PubMedGoogle Scholar
  28. 28.
    Belshe RB, Graham BS, Keefer MC, Gorse GJ, Wright P, Dolin R, Matthews T, Weinhold K, Bolognesi DP, Sposto R, Stablein DM, Twaddell T, Berman PW, Gregory T, Lzu AE, Walker MC, Fast P (1994) Neutralizing antibodies to HIV-1 in seronegative volunteers immunized with recombinant gp120 from the MN strain of HIV-1. JAMA 272:475–480PubMedGoogle Scholar
  29. 29.
    Belshe RB, Clements ML, Dolin R, Graham BS, Mlrath J, Gorse GJ, Schwartz D, Keefer MC, Wright P, Corey L, Bolognesi DP, Matthews TJ, Stablein DM, O’Brien FS, Eibl M, Dorner F, Koff W (1993) Safety and immunogenicity of a fully glycosylated recombinant gpi6o human immunodeficiency virus type 1 vaccine in subjects at low risk of infection. J Infect Dis 168:1387–1395PubMedGoogle Scholar
  30. 30.
    Gorse GJ, Schwartz DH, Graham BS, Matthews TJ, Stablein DM, Frey SE, Belshe RB, Clements ML, Wright PF, Eibl M, Fast PE (1994) HIV-1 recombinant gpi6o vaccine given in accelerated dose schedules. Clin Exp Immunol 98:178–184PubMedGoogle Scholar
  31. 31.
    Dolin R, Graham BS, Greenberg SB, Tacket CO, Belshe RB, Midthun K, Clements ML, Gorse GJ, Horgan BW, Atmar RL, Karzon DT, Bonnez W, Fernie BF, Montefiori DC, Stablein DM, Smith GE, Koff WC (1991) The safety and immunogenicity of a human immunodeficiency virus type 1 (HIV-1) recombinant gpi6o candidate vaccine in humans. Ann Int Med 114:119–127PubMedGoogle Scholar
  32. 32.
    Roberts CG, Meister GE, Jesdale BM, Lieberman J, Berzofsky JA, De Groot AS (1996) Prediction of HIV peptide epitopes by a novel algorithm. AIDS Res Hum Retroviruses 12:593–610PubMedGoogle Scholar
  33. 33.
    Deres K, Schild H, Wiesmüller K-H, Jung G, Rammensee H-G (1989) In vivo priming of virus-specific cytotoxic T lymphocytes with synthetic lipopeptide vaccine. Nature 342:561–564PubMedGoogle Scholar
  34. 34.
    Alving CR, Koulchin V, Glenn GM, Rao M (1995) Liposomes as carriers of peptide antigens: induction of antibodies and cytotoxic T lymphocytes to conjugated and unconjugated peptides. Immunol Rev 145:5–31PubMedGoogle Scholar
  35. 35.
    Ahlers JD, Dunlop N, Pendleton CD, Newman M, Nara PL, Berzofsky JA (1996) Candidate HIV type 1 multideterminant cluster peptide-P18MN vaccine constructs elicit type 1 helper T cells, cytotoxic T cells and neutralizing antibody, all using the same adjuvant immunization. AIDS Res Hum Retroviruses 12:259–272PubMedGoogle Scholar
  36. 36.
    Gorse GJ, Keefer MC, Belshe RB, Matthews TJ, Forrest BD, Hsieh RH, Koff WC, Hanson CV, Dolin R, Weinhold KJ, Frey SE, Ketter N, Fast PE (1996) A doseranging study of a prototype synthetic HIV-1 (MN) V3 branched peptide vaccine. J Infect Dis 173:330–339PubMedGoogle Scholar
  37. 37.
    Zarling JM, Eichberg JW, Moran PA, McClure J, Sridhar P, Hu S-L (1987) Proliferative and cytotoxic T cells to AIDS virus glycoproteins in chimpanzees immunized with a recombinant vaccinia virus expressing AIDS virus envelope glycoproteins. J Immunol 139:988–990PubMedGoogle Scholar
  38. 38.
    Polacino P, Stallard V, Klaniecki J, Brown C, Watanabe R, Morton WR, Benveniste RE, Hu SL (1996) Immunization with SIVmne envelope (gp160) vaccines protected macaques against intrarectal challenge by uncloned virus. XI International Conference on AIDS, Vancouver, 7–11 July 1996 (abstr no. Mo.A.103)Google Scholar
  39. 39.
    Muster T, Ferko B, Klima A, Purtscher M, Trkola A, Schulz P, Grassauer A, Engelhardt OG, Garcia-Sastre A, Palese P, Katinger H (1995) Mucosal model of immunization against human immunodeficiency virus type 1 with a chimeric influenza virus. J Virol 69:6678–6686PubMedGoogle Scholar
  40. 40.
    Berggren RE, Wunderlich A, Ziegler E, Schleicher M, Duke RC, Looney D, Fang FC (1995) HIV gp120-specific cell-mediated immune responses in mice after oral immunization with recombinant Salmonella. J Acquir Immune Defic Syndr Hum R 10:489–495Google Scholar
  41. 41.
    Aldovini A, Young RA (1991) Humoral and cell-mediated immune responses to live recombinant BCG-HIV vaccines. Nature 351:479–482PubMedGoogle Scholar
  42. 42.
    Aldovini A, Young RA (1990) Development of a BCG recombinant vehicle for candidate AIDS vaccines. Int Rev Immunol 7:79–83PubMedGoogle Scholar
  43. 43.
    Zagury D, Bernard J, Cheynier R, Desportes I, Leonard R, Fouchard M, Reveil B, Ittele D, Lurhuma Z, Mbayo K, Wane J, Salaun J-J, Goussard B, Dechazal L, Burny A, Nara P, Gallo RC (1988) A group specific anamnestic immune reaction against HIV-1 induced by a candidate vaccine against AIDS. Nature 332:728–734PubMedGoogle Scholar
  44. 44.
    Picard O, Giral P, Defer MC, Fouchard M, Morel M, Meyohas MC, Lebas J, Imbert JC, Frottier J, Salaun JJ, Lurhuma Z, Moss B, Gallo RC, Zagury D (1990) AIDS vaccine therapy: phase I trial. Lancet 336:179PubMedGoogle Scholar
  45. 45.
    Guillaume JC, Saiag P, Wechsler J, Lescs MC, Roujeau JC (1991) Vaccinia from recombinant virus expressing HIV genes. Lancet 337:1034–1035PubMedGoogle Scholar
  46. 46.
    Meyer H, Sutter G, Mayr A (1991) Mapping of deletions in the genome of the highly attenuated vaccinia virus MVA and their influence on virulence. J Gen Virol 72:1031–1038PubMedGoogle Scholar
  47. 47.
    Sutter G, Wyatt LS, Foley PL, Bennink JR, Moss B (1994) A recombinant vector derived from the host range-restricted and highly attenuated MVA strain of vaccinia virus stimulates protective immunity in mice to influenza virus. Vaccine 12:1032–1040PubMedGoogle Scholar
  48. 48.
    Tartaglia J, Perkus ME, Taylor J, Norton EK, Audonnet JC, Cox WI, Davis SW, van der Hoeven J, Meignier B, Riviere M, Languet B, Paoletti E (1992) NYVAC: a highly attenuated strain of vaccinia virus. Virology 188:217–232PubMedGoogle Scholar
  49. 49.
    Baxby D, Paoletti E (1992) Potential use of non-replicating vectors as recombinant vaccines. Vaccine 10:8–9PubMedGoogle Scholar
  50. 50.
    Taylor J, Weinberg R, Tartaglia J, Richardson C, Alkhatib G, Briedis D, Appel M, Norton E, Paoletti E (1992) Nonreplicating viral vectors as potential vaccines: recombinant canarypox virus expressing measles virus fusion (F) and hemagglutinin (HA) glycoproteins. Virology 187:321–328PubMedGoogle Scholar
  51. 51.
    Lubeck MD, Natuk RJ, Chengalvala M, Chanda PK, Murthy KK, Murthy S, Mizutani S, Lee SG, Wade MS, Bhat BM, Bhat R, Dheer SK, Eichberg JW, Davis AR, Hung PP (1994) Immunogenicity of recombinant adenovirus-human immunodeficiency virus vaccines in chimpanzees following intranasal administration. AIDS Res Hum Retroviruses 10:1443–1449PubMedGoogle Scholar
  52. 52.
    Hu S-L, Stallard V, Abrams K, Barber GN, Kuller L, Langlois AJ, Morton WR, Benveniste RE (1993) Protection of vaccinia-primed macaques against S(mne) infection by combination immunization with recombinant vaccinia virus and SIV (Mne) gp160. J Med Primatol 22:92–99PubMedGoogle Scholar
  53. 53.
    Pialoux G, Excler JL, Riviere Y, Gonzalez-Canali G, Feuillie V, Coulaud P, Gluckman JC, Matthews TJ, Meignier B, Kieny MP, Gonnet P, Diaz I, Meric C, Paoletti E, Tartaglia J, Salomon H, Plotkin S (1995) A prime-boost approach to HIV preventive vaccine using a recombinant canarypox virus expressing glycoprotein 160 (MN) followed by a recombinant glycoprotein 160 (MN/LAI). AIDS Res Hum Retroviruses 11:373–381PubMedGoogle Scholar
  54. 54.
    Perales MA, Schwartz DH, Fabry JA, Lieberman J (1995) A vaccinia-gp160-based vaccine but not a gp160 protein vaccine elicits anti-gp160 cytotoxic T lymphocytes in some HIV-1 seronegative vaccinees. J Acquir Immune Defic Syndr Hum R 10:27–35Google Scholar
  55. 55.
    Fleury B, Janvier G, Pialoux G, Buseyne F, Robertson MN, Tartaglia J, Paoletti E, Kieny MP, Excler JL, Riviere Y (1996) Memory cytotoxic T lymphocyte responses in human immunodeficiency virus type 1 (HIV-1)-negative volunteers immunized with a recombinant canarypox expressing gp160 of HIV-1 and boosted with a recombinant gp160. J Infect Dis 174:734–738PubMedGoogle Scholar
  56. 56.
    Zolla-Pazner S, Sharpe S (1995) A resting cell assay for improved detection of antibody-mediated neutralization of HIV type 1 primary isolates. AIDS Res Hum Retroviruses 11:1449–1458PubMedGoogle Scholar
  57. 57.
    Corey L, Weinhold K, Mlrath J, Excler J-L, Duliege AM, Clements ML, Belshe R, Dolin R, Graham B (1996) Safety and immunogenicity of live recombinant canarypox vector containing the envelope, gag and protease genes of HIV-1 in seronegative adult volunteers. XI International Conference on AIDS, Vancouver, 7–11 July 1996 (abstr no. Mo.A.282)Google Scholar
  58. 58.
    Haynes JR, Cao SX, Rovinski B, Sia C, James O, Dekaban GA, Klein MH (1991) Production of immunogenic HIV-1 virus-like particles in stably engineered monkey cell lines. AIDS Res Hum Retroviruses 7:17–27PubMedGoogle Scholar
  59. 59.
    Shen L, Mazzara GP, Disciullo SO, Panicali DL, Letvin NL (1993) Immunization with lentivirus-like particles elicits a potent SIV-specific recall cytotoxic lymphocyte-T response in Rhesus monkeys. AIDS Res Hum Retroviruses 9:129–132PubMedGoogle Scholar
  60. 60.
    Weber J, Cheinsong-Popov R, Callow D, Adams S, Patou G, Hodgkin K, Martin S (1995) Immunogenicity of the yeast recombinant p17/p24:Ty virus-like particles (p24-VLP) in healthy volunteers. Vaccine 13:831–834PubMedGoogle Scholar
  61. 61.
    Porter DC, Meisen LR, Compans RW, Morrow CD (1996) Release of virus-like particles from cells infected with poliovirus replicons which express human immunodeficiency virus type 1 Gag. J Virol 70:2643–2649PubMedGoogle Scholar
  62. 62.
    Truong C, Brand D, Mallet F, Roingeard P, Brunet S, Barin F (1996) Assembly and immunogenicity of chimeric Gag-Env proteins derived from the human immunodeficiency virus type 1. AIDS Res Hum Retroviruses 12:291–301PubMedGoogle Scholar
  63. 63.
    Wagner R, Demi L, Schirmbeck R, Niedrig M, Reimann J, Wolf H (1996) Construction, expression and immunogenicity of chimeric HIV-1 virus-like particles. Virology 220:128–140PubMedGoogle Scholar
  64. 64.
    Stott EJ, Chan WL, Mills KH, Page M, Taffs F, Cranage M, Greenaway P, Kitchin P (1990) Preliminary report: protection of cynomolgus macaques against simian immunodeficiency virus by fixed infected-cell vaccine. Lancet 336:1538–1541PubMedGoogle Scholar
  65. 65.
    Stott EJ (1991) Anti-cell antibody in macaques. Nature 353:393PubMedGoogle Scholar
  66. 66.
    Langlois AJ, Weinhold KJ, Matthews TJ, Greenberg ML, Bolognesi DP (1992) The ability of certain SIV vaccines to provoke reactions against normal cells. Science 255:292–293PubMedGoogle Scholar
  67. 67.
    Langlois AJ, Weinhold KJ, Matthews TJ, Greenberg ML, Bolognesi DP (1992) Detection of anti-human cell antibodies in sera from macaques immunized with whole inactivated virus. AIDS Res Hum Retroviruses 8:1641–1652PubMedGoogle Scholar
  68. 68.
    Cranage MP, Polyanskaya N, Mride B, Cook N, Ashworth LAE, Dennis M, Baskerville A, Greenaway PJ, Corcoran T, Kitchin P, Rose J, Murphey-Corb M, Desrosiers RC, Stott EJ, Farrar GH (1993) Studies on the specificity of the vaccine effect elicited by inactivated simian immunodeficiency virus. AIDS Res Hum Retroviruses 9:13–22PubMedGoogle Scholar
  69. 69.
    Dormont D, Legrand R, Cranage M, Greenaway P, Hunsmann G, Stahl-Hennig C, Rossi G, Verani P, Stott J, Kitchin P, Osterhaus A, Devries P, Kurth R, Norley S, Heeney J, Biberfeld G, Putkonen P (1995) Protection of macaques against simian immunodeficiency virus infection with inactivated vaccines: comparison of adjuvants, doses and challenge viruses. Vaccine 13:295–300Google Scholar
  70. 70.
    Chan WL, Rodgers A, Grief C, Almond N, Ellis S, Flanagan B, Silvera P, Bootman J, Stott J, Kent K, Bomford R (1995) Immunization with class I human histocompatibility leukocyte antigen can protect macaques against challenge infection with SIVmac-32H. AIDS 9:223–228PubMedGoogle Scholar
  71. 71.
    Arthur LO, Bess JW, Urban RG, Strominger JL, Morton WR, Mann DL, Henderson LE, Benveniste RE (1995) Macaques immunized with HLA-DR are protected from challenge with simian immunodeficiency virus. J Virol 69:3117–3124PubMedGoogle Scholar
  72. 72.
    Arthur LO, Bess JW, Sowder RC, Benveniste RE, Mann DL, Chermann JC, Henderson LE (1992) Cellular proteins bound to immunodeficiency viruses - implications for pathogenesis and vaccines. Science 258:1935–1938PubMedGoogle Scholar
  73. 73.
    Frank I, Stoiber H, Godar S, Stockinger H, Steindl F, Katinger HWD, Dierich MP (1996) Acquisition of host cell-surface-derived molecules by HIV-1. AIDS 10:1611–1620PubMedGoogle Scholar
  74. 74.
    Robinson HL, Lu S, Feltquate DM, Torres CT, Richmond J, Boyle CM, Morin MJ, Santoro JC, Webster RG, Montefiori D, Yasutomi Y, Letvin NL, Manson K, Wyand M, Haynes JR (1996) DNA vaccines. AIDS Res Hum Retroviruses 12:455–457PubMedGoogle Scholar
  75. 75.
    Ulmer JB, Sadoff JC, Liu MA (1996) DNA vaccines. Curr Opin Immunol 8:531–536PubMedGoogle Scholar
  76. 76.
    Whalen RG (1996) DNA vaccines, cyberspace and self-help programs. Intervirology 39:120–125PubMedGoogle Scholar
  77. 77.
    Segal BM, Shevach EM (1996) IL-12 unmasks latent autoimmune disease in resistant mice. J Exp Med 184:771–775PubMedGoogle Scholar
  78. 78.
    Desrosiers RC (1995) Non-human primate models for AIDS vaccines. AIDS 9 [Suppl A]: S137-S141PubMedGoogle Scholar
  79. 79.
    Daniel MD, Kirchhoff F, Czajak SC, Sehgal PK, Desrosiers RC (1992) Protective effects of a live attenuated SIV vaccine with a deletion in the nef gene. Science 258:1938–1941PubMedGoogle Scholar
  80. 80.
    Heeney JL, Holterman L, ten Haaft P, Dubbes R, Koornstra W, Teeuwsen V, Bourquin P, Norley S, Niphuis H (1994) Vaccine protection and reduced virus load from heterologous macaque-propagated SIV challenge. AIDS Res Hum Retroviruses 10:117–121Google Scholar
  81. 81.
    Putkonen P, Walther L, Zhang YJ, Li SL, Nilsson C, Albert J, Biberfeld P, Thorstensson R, Biberfeld G (1995) Long-term protection against SIV-induced disease in macaques vaccinated with a live attenuated HIV-2 vaccine. Nature Med 1:914–918PubMedGoogle Scholar
  82. 82.
    Almond N, Kent K, Cranage M, Rud E, Clarke B, Stott EJ (1995) Protection by attenuated simian immunodeficiency virus in macaques against challenge with virus-infected cells. Lancet 345:1342–1344PubMedGoogle Scholar
  83. 83.
    Bogers WMJM, Niphuis H, ten Haaft P, Laman JD, Koornstra W, Heeney JL (1995) Protection from HIV-1 envelope-bearing chimeric immunodeficiency virus (SHIV) in rhesus macaques infected with attenuated SIV: consequences of challenge. AIDS 9:13–18Google Scholar
  84. 84.
    Marthas ML, Miller CJ, Sutjipto S, Higgins J, Torten J, Lohman BL, Unger RE, Ramos RA, Kiyono H, McGhee JR, Marx PA, Pedersen NC (1992) Efficacy of live-attenuated and whole-inactivated simian immunodeficiency virus vaccines against vaginal challenge with virulent SIV. J Med Primatol 21:99–107PubMedGoogle Scholar
  85. 85.
    Quesada-Rolander M, Makitalo B, Thorstensson R, Zhang YJ, Castanos-Velez E, Biberfeld G, Putkonen P (1996) Protection against mucosal SIVsm challenge in macaques infected with a chimeric SIV that expresses HIV type 1 envelope. AIDS Res Hum Retroviruses 12:993–999PubMedGoogle Scholar
  86. 86.
    Deacon NJ, Tsykin A, Solomon A, Smith K, Ludford-Menting M, Hooker DJ, Mhee DA, Greenaway AL, Ellett A, Chatfield C, Lawson VA, Crowe S, Maerz A, Sonza S, Learmont J, Sullivan JS, Cunningham A, Dwyer D, Dowton D, Mills J (1995) Genomic structure of an attenuated quasi species of HIV-1 from a blood transfusion donor and recipients. Science 270:988–991PubMedGoogle Scholar
  87. 87.
    Mariani R, Kirchhoff F, Greenough TC, Sullivan JL, Desrosiers RC, Skowronski J (1996) High frequency of defective nef alleles in a long-term survivor with nonprogressive human immunodeficiency virus type 1 infection. J Virol 70:7752–7764PubMedGoogle Scholar
  88. 88.
    Travers K, Mboup S, Marlink R, Guèye-Ndiaye A, Siby T, Thior I, Traore I, Dieng-Sarr A, Sankale JL, Mullins C, Ndoye I, Hsieh CC, Essex M, Kanki P (1995) Natural protection against HIV-1 infection provided by HIV-2. Science 268:1612–1615PubMedGoogle Scholar
  89. 89.
    Biberfeld G, Thorstensson R, Putkonen P (1996) Protection against human immunodeficiency virus type 2 and simian immunodeficiency virus in macaques vaccinated against human immunodeficiency virus type 2. AIDS Res Hum Retroviruses 12:443–446PubMedGoogle Scholar
  90. 90.
    Whatmore AM, Cook N, Hall GA, Sharpe S, Rud EW, Cranage MP (1995) Repair and evolution of nef in vivo modulates simian immunodeficiency virus virulence. J Virol 69:5117–5123PubMedGoogle Scholar
  91. 91.
    Shiramizu B, Herndier BG, McGrath MS (1994) Identification of a common clonal human immunodeficiency virus integration site in human immunodeficiency virus-associated lymphomas. Cancer Res 54:2069–2072PubMedGoogle Scholar
  92. 92.
    Chakrabarti BK, Maitra RK, Ma XZ, Kestler HW (1996) A candidate live inactivatable attenuated vaccine for AIDS. Proc Natl Acad Sci USA 93:9810–9815PubMedGoogle Scholar
  93. 93.
    Baba TW, Jeong YS, Penninck D, Bronson R, Greene MF, Ruprecht RM (1995) Pathogenicity of live, attenuated SIV after mucosal infection of neonatal macaques. Science 267:1820–1825PubMedGoogle Scholar
  94. 94.
    Wyand MS, Manson KH, Lackner AA, Desrosiers RC (1997) Resistance of neonatal monkeys to live attenuated vaccine strains of simian immunodeficiency virus. Nat Med 3:32–36PubMedGoogle Scholar
  95. 95.
    Pantaleo G, Fauci AS (1995) New concepts in the immunopathogenesis of HIV infection. Annu Rev Immunol 13:487–512PubMedGoogle Scholar
  96. 96.
    Cao YZ, Qin LM, Zhang LQ, Safrit J, Ho DD (1995) Virologie and immunologic characterization of long-term survivors of human immunodeficiency virus type 1 infection. N Engl J Med 332:201–208PubMedGoogle Scholar
  97. 97.
    Brostrom C, Sonnerborg A, Sallberg M (1995) Human immunodeficiency virus type 1-infected patients with no disease progression display high-avidity antibody production to autologous V3 sequences. J Infect Dis 171:509–511PubMedGoogle Scholar
  98. 98.
    Hogervorst E, Jurriaans S, Dewolf F, Vanwijk A, Wiersma A, Valk M, Roos M, Vangemen B, Coutinho R, Miedema F, Goudsmit J (1995) Predictors for non- and slow progression in human immunodeficiency virus (HIV) type 1 infection: low viral RNA copy numbers in serum and maintenance of high HIV-1 P24- specific but not V3-specific antibody levels. J Infect Dis 171:811–821PubMedGoogle Scholar
  99. 99.
    Barker E, Mackewicz CE, Levy JA (1995) Effects of T(H)i and T(H)2 cytokines on CD8(+) cell response against human immunodeficiency virus: implications for long-term survival. Prot Natl Acad Sci USA 92:11135–11139Google Scholar
  100. 100.
    Harrer T, Harrer E, Kalams SA, Elbeik T, Staprans SI, Feinberg MB, Cao YZ, Ho DD, Yilma T, Caliendo AM, Johnson RP, Buchbinder SP, Walker BD (1996) Strong cytotoxic T cell and weak neutralizing antibody responses in a subset of persons with stable nonprogressing HIV type 1 infection. AIDS Res Hum Retroviruses 12:585–592PubMedGoogle Scholar
  101. 101.
    Zanussi S, Dandrea M, Simonelli C, Tirelli U, Depaoli P (1996) Serum levels of RANTES and MIP-1 alpha in HIV-positive long-term survivors and progressor patients. AIDS 10:1431–1432PubMedGoogle Scholar
  102. 102.
    Clerici M, Shearer GM (1996) Correlates of protection in HIV infection and the progression of HIV infection to AIDS. Immunol Lett 51:69–73PubMedGoogle Scholar
  103. 103.
    Bryson YJ, Pang S, Wei LS, Dickover R, Diagne A, Chen ISY (1995) Clearance of HIV infection in a perinatally infected infant. N Engl J Med 332:833–838PubMedGoogle Scholar
  104. 104.
    Mcintosh K, Burchett SK (1995) Clearance of HIV - lessons from newborns. N Engl J Med 332:883–884PubMedGoogle Scholar
  105. 105.
    Roques PA, Gras G, Parnetmathieu F, Mabondzo AM, Dollfus C, Narwa R, Marce D, Tranchotdiallo J, Herve F, Lasfargues G, Courpotin C, Dormont D (1995) Clearance of HIV infection in 12 perinatally infected children: clinical, virological and immunological data. AIDS 9:19–26Google Scholar
  106. 106.
    Newell ML, Dunn D, Demaria A, Ferrazin A, Dossi A, Giaquinto C, Levy J, Alimenti A, Ehrnst A, Bohlin AB, Ljung R, Peckham C (1996) Detection of virus in vertically exposed HIV-antibody-negative children. Lancet 347:213–215PubMedGoogle Scholar
  107. 107.
    Shearer GM, Clerici M (1996) Protective immunity against HIV infection: has nature done the experiment for us? Immunol Today 17:21–24PubMedGoogle Scholar
  108. 108.
    Paxton WA, Martin SR, Tse D, O’Brien TR, Skurnick J, Vaevanter NL, Padian N, Braun JF, Kotler DP, Wolinsky SM, Koup RA (1996) Relative resistance to HIV-1 infection of CD4 lymphocytes from persons who remain uninfected despite multiple high-risk sexual exposures. Nature Med 2:412–417PubMedGoogle Scholar
  109. 109.
    Lohman BL, McChesney MB, Miller CJ, Otsyula M, Berardi CJ, Marthas ML (1994) Mucosal immunization with a live, virulence-attenuated simian immunodeficiency virus (SIV) vaccine elicits antiviral cytotoxic T-lymphocytes and antibodies in rhesus macaques. J Med Primatol 23:95–101PubMedGoogle Scholar
  110. 110.
    Mestecky J, Jackson S (1994) Reassessment of the impact of mucosal immunity in infection with the human immunodeficiency virus (HIV) and design of relevant vaccines. J Clin Immunol 14:259–272PubMedGoogle Scholar
  111. 111.
    Kiyono H, Miller CJ, Lu YC, Lehner T, Cranage M, Huang YT, Kawabata S, Marthas M, Roberts B, Nedrud JG, Lamm ME, Bergmeier L, Brookes R, Tao L, McGhee JR (1995) The common mucosal immune system for the reproductive tract: basic principles applied toward an AIDS vaccine. Adv Drug Delivery Rev 18:23–52Google Scholar
  112. 112.
    Miller CJ, McGhee JR (1996) Progress towards a vaccine to prevent sexual transmission of HIV. Nature Med 2:751–752PubMedGoogle Scholar
  113. 113.
    Lehner T, Wang YF, Cranage M, Bergmeier LA, Mitchell E, Tao L, Hall G, Dennis M, Cook N, Brookes R, Klavinskis L, Doyle C, Ward R (1996) Protective mucosal immunity elicited by targeted iliac lymph node immunization with a subunit SIV envelope and core vaccine in macaques. Nature Med 2:767–775PubMedGoogle Scholar
  114. 114.
    Salvato MS, Emau P, Malkovsky M, Schultz KT, Johnson E, Pauza CD (1994) Cellular immune responses in rhesus macaques infected rectally with low dose simian immunodeficiency virus. J Med Primatol 23:125–130PubMedGoogle Scholar
  115. 115.
    Clerici M, Clark EA, Polacino P, Axberg I, Kuller L, Casey NI, Morton WR, Shearer GM, Benveniste RE (1994) T-cell proliferation to subinfectious SIV correlates with lack of infection after challenge of macaques. AIDS 8:1391–1395PubMedGoogle Scholar
  116. 116.
    Ruprecht RM, Baba TW, Li A, Ayehunie S, Hu YW, Liska V, Rasmussen R, Sharma PL (1996) Live attenuated HIV as a vaccine for AIDS: pros and cons. Semin Virol 7:147–155Google Scholar

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© Springer-Verlag Berlin Heidelberg 1998

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  • J. W. Mannhalter

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