Información del artículo
El avance de la epidemia del síndrome de inmunodeficiencia adquirida (SIDA) ha situado la obtención de una vacuna eficaz frente al virus de la inmunodeficiencia humana (VIH) como un objetivo científico prioritario. En el momento actual no se dispone de una vacuna preventiva 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 particular 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, esta investigación se sitúa 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
Respuesta inmunitaria
Vacunas
Escape viral
The AIDS epidemic continues to advance, and the development of a preventive HIV vaccine has become a major objective for scientific research. An effective vaccine against this virus is not available and complete protection still has not been achieved in animal models. In this review the major challenges related to the development of a vaccine against HIV are analyzed, particularly the mechanisms involved in viral escape from the immune response, and the results obtained with the various therapeutic and preventive vaccine prototypes are summarized. Finally, the social, economic and health aspects related to research on HIV vaccines and the current controversy around the performance of clinical trials with these agents is discussed.
Keywords:
HIV
AIDS
Immune response
Vaccines
Viral escape
El Texto completo está disponible en PDF
Bibliografía
[1.]
G.J.V. Nossal.
The Global Alliance for Vaccines and Immunization: A millennial challenge.
Nature Immunol, 1 (2000), pp. 1-8
[3.]
J. Esparza, N. Bhamarapravati.
Accelerating the development and future availability of HIV-1 vaccines: Why, when, where, and how?.
Lancet, 355 (2000), pp. 2061-2066
[4.]
G.J. Nabel.
Challenges and opportunities for development of an AIDS vaccines.
Nature, 410 (2001), pp. 1002-1006
[5.]
Corey L. HIV preventive vaccines: Science and politics. XIV International AIDS Conference. Barcelona, Spain, July 2002 [Abstract n.° 143]
[6.]
P. Piot.
Global AIDS Epidemic: Time to Turn the Tide.
Science, 228 (2000), pp. 2176-2178
[7.]
J. Cohen.
South Africa’s New Enemy.
Science, 228 (2000), pp. 2168-2170
[8.]
WHO. UNAIDS report on the global HIV/AIDS epidemic.
WHO, (2002),
[9.]
R. Zinkernagel, P. Doherty.
MHC-restricted cytotoxic T-cells: Studies on the biological role of major transplantation antigens determining T-cell restriction-specificity, function and responsiveness.
Adv Immunol, 27 (2000), pp. 51-177
[10.]
C.A.Jr. Janeway, P. Travers, M. Walport, J. Donald.
Inmunobiología.
El sistema inmunitario en condiciones de salud y enfermedad,
[11.]
B.N. Fields, D.M. Knipe, P.M. Howley.
Virology.
Lippincott-Raven, (1996),
[12.]
M. Robert-Guroff, M. Brown, R.C. Gallo.
HTLV-III-neutralizing antibodies in patients with AIDS and AIDS-related complex.
Nature, 316 (1985), pp. 72-74
[13.]
G.J. Nabel, J. Sullivan.
Antibodies and Resistance to Natural HIV Infection.
N Engl J Med, 343 (2000), pp. 17-19
[14.]
J.C. Bandrés, S. Zolla-Pazner.
Inmunidad humoral en la infección por el VIH.
Infección por el VIH 1999,
[15.]
T. Igarashi.
Human immunodeficiency virus type 1 neutralizing antibodies accelerate clearance of cell-free virions from blood plasma.
Nat Med, 5 (1999), pp. 211-216
[16.]
R. Shibata.
Neutralizing antibody directed against the HIV-1 envelope glucoprotein can completely block HIV-1/SIV chimeric virus infections of macaque monkeys.
Nat Med, 5 (1999), pp. 204-210
[17.]
J.R. Mascola, G. Stiegler, T.C. VanCott, H. Katinger, C.B. Carpenter, C.E. Hanson, et al.
Protection of macaques against vaginal transmission of a pathogenic HIV-1/SIV chimeric virus by passive infusion of neutralizing antibodies.
Nat Med, 6 (2000), pp. 207-210
[18.]
T.W. Baba, V. Liska, R. Hofmann-Lehmann, J. Vlasak, W. Xu, S. Ayehunie, et al.
Human neutralizing monoclonal antibodies of the IgG1 subtype protect against mucosal simian-human immunodeficiency virus infection.
Nat Med, 6 (2000), pp. 200-206
[19.]
Richman DD, Wrin T, Little S, Petropoulos C. Rapid evolution of the neutralizing antibody response following primary HIV infection. XIV International AIDS Conference. Barcelona, Spain, July 2002 [Abstract n.° 1051]
[20.]
H.L. Robinson, D.C. Montefiori, R.P. Johnson, K.H. Manson, M.L. Kalish, J.D. Lifson, et al.
Neutralizing antibody-independent containment of immunodeficiency virus challenges by DNA priming and recombinant pox virus booster immunizations.
Nat Med, 5 (1999), pp. 526-534
[21.]
P. Poignard.
Neutralizing antibodies have limited effects on the control of established HIV-1 infections in vivo.
Immunity, 10 (1999), pp. 431-438
[22.]
J.P. Moore, D.R. Burton.
HIV-1 neutralizing antibodies: How full is the bottle?.
Nat Med, 5 (1999), pp. 142-144
[23.]
Q. Sattentau.
Neutralization of HIV-1 by antibody.
Curr Opin Immunol, 8 (1996), pp. 540-545
[24.]
D.R. Burton.
A vaccine for HIV type 1: The antibody perspective.
Proc Natl Acad Sci USA, 94 (1997), pp. 10018-10023
[25.]
D.R. Burton.
Opinion: Antibodies, viruses and vaccines.
Nat Rev Immunol, 2 (2002), pp. 706-713
[26.]
Burton D. Human neutralizing antibodies and a vaccine for HIV-1. XIV International AIDS Conference. Barcelona, Spain, July 2002 [Abstract n.° 201]
[27.]
R. Wyatt, J. Sodroski.
The HIV-1 envelope glycoproteins: Fusogens, antigens, and immunogens.
Science, 280 (1998), pp. 1884-1888
[28.]
Desrosiers R. Factors that determine neutralization resistance of SIV: Are there lessons to be learned on how to elicit antibodies with broadly neutralizing activity against primary isolates of HIV-1 XIV International AIDS Conference. Barcelona, Spain, July 2002 [Abstract n.° 209]
[29.]
C.N. Scanlan, R. Pantophlet, M.R. Wormald, E. Ollmann Saphire, R. Stanfield, I.A. Wilson, et al.
The broadly neutralizing anti-human immunodeficiency virus type 1 antibody 2G12 recognizes a cluster of alpha1– >2 mannose residues on the outer face of gp120.
J Virol, 76 (2002), pp. 7306-7321
[30.]
M. Moulard, S.K. Phogat, Y. Shu, A.F. Labrijn, X. Xiao, J.M. Binley, et al.
Broadly cross-reactive HIV-1-neutralizing human monoclonal Fab selected for binding to gp120-CD4-CCR5 complexes.
Proc Natl Acad Sci USA, 99 (2002), pp. 6913-6918
[31.]
M.B. Zwick, M. Wang, P. Poignard, G. Stiegler, H. Katinger, D.R. Burton, et al.
Neutralization synergy of human immunodeficiency virus type 1 primary isolates by cocktails of broadly neutralizing antibodies.
J Virol, 75 (2001), pp. 12198-12208
[32.]
M.B. Zwick, A.F. Labrijn, M. Wang, C. Spenlehauer, E.O. Saphire, J.M. Binley, et al.
Broadly neutralizing antibodies targeted to the membrane-proximal external region of human immunodeficiency virus type 1 glycoprotein gp41.
J Virol, 75 (2001), pp. 10892-10905
[33.]
A.J. McMichael, S.L. Rowland-Jones.
Cellular immune responses to HIV.
Nature, 410 (2001), pp. 980-987
[34.]
G.S. Ogg, X. Jin, S. Bonhoeffe, R.P. Dunbar, M.A. Nowak, S. Monard, et al.
Quantitation of HIV-1-specific cytotoxic T lymphocytes and plasma load of viral RNA.
Science, 279 (1998), pp. 2103-2106
[35.]
E.S. Rosenberg, J.M. Billingsley, A.M. Caliendo, S.L. Boswell, P.E. Sax, S.A. Kalams, et al.
Vigorous HIV-1-specific CD4+ T cell responses associated with control of viremia.
Science, 278 (1997), pp. 1447-1450
[36.]
E.S. Rosenberg, M. Altfeld, S.H. Poon, M.N. Phillips, B.M. Wilkes, R.L. Eldridge, et al.
Immune control of HIV-1 after early treatment of acute infection.
Nature, 407 (2000), pp. 523-526
[37.]
S.A. Ghanekar, S.A. Stranford, J.C. Ong, J.M. Walker, V.C. Maino, J.A. Levy.
Decreased HIV-specific CD4 T cell proliferation in long-term HIV-infected individuals on antiretroviral therapy.
AIDS, 15 (2001), pp. 1885-1887
[38.]
C.J. Pitcher.
HIV-1-specific CD4+ T cells are detectable in most individuals with active HIV-1 infection, but decline with prolonged viral suppression.
Nature Med, 5 (1999), pp. 518-525
[39.]
C.M. Gray.
Frequency of class I HLA-restricted anti-HIV CD8+ T cells in individuals receiving highly active antiretroviral therapy (HAART.
J Immunol, 162 (1999), pp. 1780-1788
[40.]
G.M. Ortiz, D.F. Nixon, A. Trkola.
HIV-1-specific immune responses in subjects who temporarily contain virus replication after discontinuation of highly active antiretroviral therapy.
J Clin Invest, 104 (1999), pp. R13-18
[41.]
F. Garcia, M. Plana, C. Vidal, A. Cruceta, W.A. O’Brien, G. Pantaleo, et al.
Dynamics of viral load rebound and immunological changes after stopping effective antiretroviral therapy.
AIDS, 13 (1999), pp. F79-86
[42.]
D. Richman.
The challenge of immune control of immunodeficiency virus.
J Clin Invest, 104 (1999), pp. 677-678
[43.]
L. Musey, J. Hughes, T. Schacker, T. Shea, L. Corey, M.J. McElrath.
Control of viremia in simian immunodeficiency virus infection by CD8+ lymphocytes.
Science, 283 (1999), pp. 857-860
[44.]
X. Jin, D.E. Bauer, S.E. Tuttleton, S. Lewin, A. Gettie, J. Blanchard, et al.
Dramatic rise in plasma viremia after CD8(+) T cell depletion in simian immunodeficiency virus-infected macaques.
J Exp Med, 189 (1999), pp. 991-998
[45.]
K.J. Metzner, X. Jin, F.V. Lee, A. Gettie, D.E. Bauer, M. Di Mascio, et al.
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, 191 (2000), pp. 1921-1931
[46.]
C.M. Walker, D.J. Moody, D.P. Stites, J.A. Levy.
CD8+ lymphocytes can control HIV infection in vitro by suppressing virus replication.
Science, 234 (1986), pp. 1563-1566
[47.]
O.O. Yang, S.A. Kalams, A. Trocha, H. Cao, A. Luster, R.P. Johnson, et al.
Suppression of human immunodeficiency virus type 1 replication by CD8+ cells: Evidence for HLA class I-restricted triggering of cytolytic and noncytolytic mechanisms.
J Virol, 71 (1997), pp. 3120-3128
[48.]
C.E. Mackewicz, D.J. Blackbourn, J.A. Levy.
CD8+ T cells suppress human immunodeficiency virus replication by inhibiting viral transcription. Proc.
Natl Acad Sci USA, 92 (1995), pp. 2308-2312
[49.]
S. Le Borgne, M. Fevrier, C. Callebaut.
CD8(+)-Cell antiviral factor activity is not restricted to human immunodeficiency virus (HIV)-specific T cells and can block HIV replication after initiation of reverse transcription.
J Virol, 74 (2000), pp. 4456-4464
[50.]
F. Cocchi, A.L. DeVico, A. Garzino-Demo, S.K. Arya, R.C. Gallo, P. Lusso.
Identification of RANTES, MIP-1 alpha, and MIP-1 beta as the major HIV-suppressive factors produced by CD8+ T cells.
Science, 270 (1995), pp. 1811-1815
[51.]
E. Oberlin, A. Amara, F. Bachelerie.
The CXC chemokine SDF-1 is the ligand for LESTR/fusin and prevents infection by T-cell-line-adapted HIV-1.
Nature, 382 (1996), pp. 833-835
[52.]
W.W. Agace, A. Amara, A.I. Roberts.
Constitutive expression of stromal derived factor-1 by mucosal epithelia and its role in HIV transmission and propagation.
Curr Biol, 10 (2000), pp. 325-328
[53.]
M. Bermejo, J. Martin Serrano, J. Alonso, J.L. Pablos, C. Gamallo, F. Arenzana, et al.
SDF-1 production by dendritic cells and regulation of CXCR4 in T lymphocytes.
XIV International AIDS Conference, Barcelona, (July 2002),
[54.]
E. Barker, K.N. Bossart, J.A. Levy.
Primary CD8+ cells from HIV-infected individuals can suppress productive infection of macrophages independent of beta-chemokines.
tProc Natl Acad Sci USA, 95 (1998), pp. 1725-1729
[55.]
S.F. Lacey, C.B. McDanal, R. Horuk, M.L. Greenberg.
The CXC chemokine stromal cell-derived factor I is not responsible for CD8+ T cell suppression of syncytia-inducing strains of HIV-1.
Proc Natl Acad Sci USA, 94 (1997), pp. 9842-9847
[56.]
Zhang L, Yu W, He T, Yu J, Caffrey RE, Dalmasso E, et al. Contribution of human _-Defensin-1, -2 and -3 to the anti-HIV activity of CD8 antiviral factor. Science. 2002 Sep 26 [epub ahead of print. www.sciencexpress.org
[57.]
S. Rowland-Jones, J. Sutton, K. Ariyoshi, T. Dong, F. Gotch, S. McAdam, et al.
HIV-specific cytotoxic T-cells in HIV-exposed but uninfected Gambian women.
Nat Med, 1 (1995), pp. 59-64
[58.]
R. Kaul, S. Rowland-Jones, J. Kimani, K. Fowke, T. Dong, P. Kiama, et al.
New insights into HIV-1 specific cytotoxic T-lymphocyte responses in exposed, persistently seronegative Kenyan sex workers.
Immunol Lett, 79 (2001), pp. 3-13
[59.]
R. Kaul, S.L. Rowland-Jones, J. Kimani, T. Dong, H.B. Yang, P. Kiama, et al.
Late seroconversion in HIV-resistant Nairobi prostitutes despite pre-existing HIV-specific CD8+ responses.
J Clin Invest, 107 (2001), pp. 341-349
[60.]
S. Mazzoli, D. Trabattoni, S. Lo Caputo, M.l. Clerici.
HIV-specific mucosal and cellular immunity in HIV-seronegative partners of HIV-seropositive individuals.
Nature Med, 3 (1997), pp. 1250-1257
[61.]
C. Devito, K. Broliden, R. Kaul, L. Stevensson, K. Johansen, P. Kiama, et al.
Mucosal and Plasma IgA from HIV-1-Exposed Uninfected Individuals Inhibit HIV-1 Transcytosis Across Human Epithelial Cells.
J Immunol, 165 (2000), pp. 5170-5176
[62.]
Y. Cao, L. Quin, J. Safrit.
Virologic and immunologic characterization of the long term survivors of HIV-1 infection.
N Engl J Med, 332 (1995), pp. 201-208
[63.]
G. Pantaleo, S. Menzo, M. Vaccarezza.
Studies in subjects with long-term non progressive HIV infection.
N Engl J Med, 332 (1995), pp. 209-216
[64.]
C. Rinaldo, X.L. Huang, Z.F. Fan, M. Ding, L. Beltz, A. Logar, et al.
High levels of anti-human immunodeficiency virus type 1 (HIV-1) memory cytotoxic T-lymphocyte activity and low viral load are associated with lack of disease in HIV-1-infected long-term nonprogressors.
J Virol, 69 (1995), pp. 5838-5842
[65.]
M.R. Klein, C.A. Van Baalen, A.M. Holwerda, S.R. Kerkhof, R.J. Garde, I.P. Bende, et al.
Kinetics of Gag-specific cytotoxic T lymphocyte responses during the clinical course of HIV-1 infection: A longitudinal analysis of rapid progressors and long-term asymptomatics.
J Exp Med, 181 (1995), pp. 1365-1372
[66.]
L. Musey, J. Hughes, T. Schacker, T. Shea, L. Corey, M.J. McElrath.
Cytotoxic-T-cell responses, viral load, and disease progression in early human immunodeficiency virus type 1 infection.
N Engl J Med, 337 (1997), pp. 1267-1274
[67.]
Autran B. Immune responses in long term non progressors. Lessons for Immune Reconstitution XIV International AIDS Conference. Barcelona, Spain, July 2002 [Abstract n.° 199]
[68.]
C. Brander, B.D. Walker.
T lymphocyte responses in HIV-1 infection: Implications for vaccine development.
Curr Opin Immunol, 11 (1999), pp. 451-459
[69.]
G. Pantaleo, H. Soudeyns, F. Demarest.
Evidence for a rapid disappearance of initially expanded HIV-specific CD8+ T cell clone during primary HIV infection.
Proc Natl Acad Sci USA, 94 (1997), pp. 9848-9853
[70.]
P.J. Goulder, M.A. Altfeld, E.S. Rosenberg, T. Nguyen, Y. Tang, R.L. Eldridge, et al.
Substantial differences in specificity of HIV-specific cytotoxic T cells in acute and chronic HIV infection.
J Exp Med, 193 (2001), pp. 181-194
[71.]
S.A. Ghanekar, S.A. Stranford, J.C. Ong, J.M. Walker, V.C. Maino, J.A. Levy.
Decreased HIV-specific CD4 T cell proliferation in long-term HIV-infected individuals on antiretroviral therapy.
AIDS, 15 (2001), pp. 1885-1887
[72.]
D. O’Connor, T.M. Hallen, T.U. Vogel, P. Jing, I.P. DeSouza, E. Dodds, et al.
Acute phase citotoxic T lymphocyte escape is a hallmarg of simian immunodeficiency virus infection.
Nature Med, 8 (2002), pp. 493-499
[73.]
A. Holguin, B. Rodes, V. Soriano.
Recombinant human immunodeficiency viruses type 1 circulating in Spain.
AIDS Res Hum Retroviruses, 16 (2000), pp. 505-511
[74.]
M.M. Thomson, M.L. Villahermosa, E. Vazquez-de-Parga.
Widespread circulation of a B/F intersubtype recombinant form among HIV-1-infected individuals in Buenos Aires, Argentina.
AIDS, 14 (2000), pp. 897-899
[75.]
G. Van der Groen, P.N. Nyambi, E. Beirnaert, D. Davis, K. Fransen, L. Heyndrickx, et al.
Genetic variation of HIV type 1: Relevance of interclade variation to vaccine development.
AIDS Res Hum Retroviruses, 14 (1998), pp. S211-221
[76.]
Workshop Report from the European Commission (DG XII, INCO-DC) and the Joint United Nations Programme on HIV/AIDS. HIV-1 subtypes: Implications for epidemiology, pathogenicity, vaccines and diagnostics.
AIDS, 11 (1997),
[77.]
C. Stahl-Hennig, R.M. Steinman, K. Tenner-Racz, M. Pope, N. Stolte, K. Mätz-Rensing, et al.
Rapid infection of oral mucosal-associated lymphoid tissue with simian immunodeficiency virus.
Science, 285 (1999), pp. 1261-1265
[78.]
A.T. Haase.
Population biology of HIV-1 infection: Viral and CD4+ T cell demographics and dynamics in lymphatic tissues.
Annu Rev Immunol, 17 (1999), pp. 625-656
[79.]
L. Zhang, B. Ramratnam, K. Tenner-Racz, Y. He, M. Vesanen, S. Lewin, et al.
Quantifying Residual HIV-1 Replication in Patients Receiving Combination Antiretroviral Therapy.
N Engl J Med, 340 (1999), pp. 1605-1613
[80.]
M.R. Furtado, D.S. Callaway, J.P. Phair, K.J. Kunstman, J.L. Stanton, C.A. Macken, et al.
Persistence of HIV-1 Transcription in Peripheral-Blood Mononuclear Cells in Patients Receiving Potent Antiretroviral Therapy.
N Engl J Med, 340 (1999), pp. 1614-1622
[81.]
R.J. Pomerantz.
Residual HIV-1 Disease in the Era of Highly Active Antiretroviral Therapy.
N Engl J Med, 340 (1999), pp. 1625
[82.]
D. Finzi, J. Blankson, J.D. Siliciano, J.B. Margolick, K. Chadwick, T. Pierson, et al.
Latent infection of CD4+ T cells provides a mechanism for lifelong persistence of HIV-1, even in patients on effective combination therapy.
Nat Med, 5 (1999), pp. 512-517
[83.]
J.N. Blankson, D. Persaud, R.F. Siliciano.
The challenge of viral reservoirs in HIV-1 infection.
Annu Rev Med, 53 (2002), pp. 557-593
[84.]
T.B. Geijtenbeek, D.S. Kwon, R. Torensma, S.J. Van Vliet, G.C. Van Duijnhouen, J. Middel, et al.
DC-SIGN, a dendritic cell-specific HIV-1-binding protein that enhances trans-infection of T cells.
Cell, 100 (2000), pp. 587-597
[85.]
R. Förster, A. Schubel, D. Breitfeld, E. Kremmer, I. Renner-Muller, E. Wolf, et al.
CCR7 Coordinates the Primary Immune Response by Establishing Functional Microenvironments in Secondary Lymphoid Organs.
Cell, 99 (1999), pp. 23-33
[86.]
D.C. Douek, J.M. Brenchley, M.R. Betts, D.R. Ambrozak, B.J. Hill, Y. Okamoto, et al.
HIV preferentially infects HIV-specific CD4+ T cells.
Nature, 417 (2002), pp. 95-98
[87.]
Siliciano R. Prospects for eradication or Long-Term control of HIV infection. XIV International AIDS Conference. Barcelona, Spain, July 2002 [Abstract n.° 103]
[88.]
M.D. Daniel, F. Kirchhoff, S.C. Czajak, P.K. Sehgal, R.C. Desrosiers.
Protective effects of a live attenuated SIV vaccine with a deletion in the nef gene.
Science, 258 (1992), pp. 1938-1941
[89.]
M.L. Murphey-Corb.
Inactivated whole SIV vaccine confers protection in macaques.
Science, 246 (1989), pp. 1293-1297
[90.]
N. Almond, J. Rose, R. Sangster, P. Silvera, B. Stebbings, Walker, et al.
Mechanisms of protection induced by attenuated simian immunodeficiency virus. Protection cannot be transferred by human serum.
J Gen Virol, 78 (1997), pp. 1919-1922
[91.]
M.C. Gauduin, R.L. Glickman, R. Means, R.P. Johnson.
Inhibition of simian immunodeficiency virus (SIV) replication by CD8+ T lymphocytes from macaques immunized with live attenuated SIV.
J Virol, 72 (1998), pp. 6315-6324
[92.]
R.P. Johnson, R.L. Glickman, J.Q. Yang, A. Kaur, J.T. Dion, M.J. Mulligan, et al.
Induction of vigorous cytotoxic T-lymphocyte responses by live attenuated simian immunodeficiency virus.
J Virol, 71 (1997), pp. 7711-7718
[93.]
R.C. Desrosiers, J.D. Lifson, J.S. Gibbs, S.C. Czajak, A.Y. Howe, L.O. Arthur, et al.
Identification of highly attenuated mutants of simian immunodeficiency virus.
J Virol, 72 (1998), pp. 1431-1437
[94.]
J.C. Learmont, A.F. Geczy, J. Mills, L.J. Ashton, C.H. Raynes-Greenow, R.J. Garsia, et al.
Immunologic and virologic status after 14 to 18 years of infection with an attenuated strain of HIV-1: A report from the Sydney Blood Bank Cohort.
N Engl J Med, 340 (1999), pp. 1715-1721
[95.]
W.B. Dyer, G.S. Ogg, M.A. Demoitie.
Strong human immunodeficiency virus (HIV-) specific cytotoxic T-lymphocyte activity in Sydney Blood Bank Cohort patients infected with nef-defective HIV type 1.
J Virol, 73 (1999), pp. 436-443
[96.]
N.J. Deacon, A. Tsykin, A. Solomon, et al.
Genomic structure of an attenuated quasi species of HIV-1 from a blood transfusion donor and recipients.
Science, 270 (1995), pp. 988-991
[97.]
R. Oelrichs, A. Tsykin, D. Rhodes, A. Solomon, A. Ellet, D. McPhee, et al.
Genomic sequence of HIV type 1 from four members of the Sydney Blood Bank Cohort of long-term nonprogressors.
AIDS Res Hum Retroviruses, 14 (1998), pp. 811-914
[98.]
R.C. Desrosiers.
Yes it is time to consider use of a live-attenuated virus vaccine against HIV-1. En: Controversies in science: A live-virus AIDS vaccine?.
J NIH Res, 6 (1994), pp. 1-4
[99.]
T.W. Baba, V. Liska, A.H. Khimani.
Live-attenuated, multiply deleted SIV causes AIDS in infants and adult macaques.
Nat Med, 5 (1995), pp. 194-203
[100.]
T.C. Greenough, L. Sullivan, R.C. Desrosiers.
Declining CD4 T-cell counts in a person infected with nef-deleted HIV-1.
N Engl J Med, 340 (1999), pp. 236-237
[101.]
E.T. Sawai, M.S. Hamza, M. Ye, K.E. Shaw, P.A. Luciw.
Pathogenic conversion of live attenuated SIV vaccine is associated with expression of truncated Nef.
J Virol, 74 (2000), pp. 2038-2045
[102.]
R.M. Ruprecht, T.W. Baba, V. Liska, S. Ayehunie, J. Andersen, D.C. Montefiori, et al.
Attenuated HIV vaccine: Caveats.
Science, 271 (1996), pp. 1790-1792
[104.]
M.L. Murphey-Corb.
Inactivated whole SIV vaccine confers protection in macaques.
Science, 246 (1989), pp. 47-1293
[105.]
D.P. Francis, T. Gregory, M.J. McElrath.
Advancing AIDSVAX to phase 3. Safety, immunogencity, and plans for phase 3.
AIDS Res Hum retroviruses, 14 (1998), pp. 25-31
[106.]
J.R. Mascola, S.W. Snyder, O.S.l. Weislow.
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 (1996), pp. 34-48
[107.]
D.P. Bolognesi, T.J. Matthews.
HIV vaccines. Viral envelope fails to deliver?.
Nature, 391 (1998), pp. 38-39
[108.]
S. Nitayaphan, A.E. Brown.
Preventive HIV vaccine development in Thailand.
AIDS, (1998), pp. 55-61
[109.]
P.W. Berman, W. Huang, L. Riddle.
Development of bivalent (B/E) vaccines able to neutralize CCR5-dependent viruses from the United States and Thailand.
Virology, 265 (1999), pp. 1-917
[110.]
R.C. Gallo.
Tat as one key to HIV-induced immune pathogenesis and Tat toxoid as an important component of a vaccine.
Proc Natl Acad Sci USA, 96 (1999), pp. 8324-8326
[111.]
A. Cafaro, A. Caputo, C. Fracasso, M.T. Maggiorella, D. Goletti, S. Baroncelli, et al.
Control of SHIV-89.6P-infection of cynomolgus monkeys by HIV-1 Tat protein vaccine.
Nat Med, 5 (1999), pp. 643-650
[112.]
E. Caselli, M. Betti, M.P. Grossi, P.G. Balboni, C. Rossi, C. Boarini, et al.
DNA immunization with HIV-1 tat mutated in the trans activation domain induces humoral and cellular immune responses against wild-type Tat.
J Immunol, 162 (1999), pp. 5631-5638
[113.]
A.D. Osterhaus, C.A. Van Baalen, R.A. Gruters, M. Schutten, C.H. Siebelink, E.G. Hulskotte, et al.
Vaccination with Rev and Tat against AIDS.
Vaccine, 17 (1999), pp. 2713-2714
[114.]
A. Gringeri, E. Santagostino, M. Muça-Perja, H. Le Buanec, B. Bizzini, A. Lachgar, et al.
Tat toxoid as a component of a preventive vaccine in seronegative subjects.
J Acquir Immune Defic Syndr Hum Retrovirol, 20 (1999), pp. 371-375
[115.]
C.D. Pauza, P. Trivedi, M. Wallace, T.J. Ruckwardt, H. Le Buanec, W. Lu, et al.
Vaccination with tat toxoid attenuates disease in simian/HIV-challenged macaques.
Proc Natl Acad Sci USA, 97 (2000), pp. 3515-3519
[116.]
H. Bukawa, K. Sekigawa, K. Hamajima, J. Fujushima, Y. Yamada, H. Kiyono, et al.
Neutralization of HIV-1 by secretory IgA induced by oral immunization with a new macromolecular multicomponent peptide vaccine candidate.
Nature Med, 1 (1995), pp. 681-685
[117.]
T.G. Evans, M.C. Keefer, K.J. Weinhold, M. Wolff, D. Montefiori, G.J. Gorse, et al.
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, 180 (1999), pp. 290-308
[118.]
J. Tartaglia, J.L. Excler, R. El Habib, K. Limbach, B. Meignier, S. Plotkin, et al.
Canarypox virus-based vaccines: Prime-boost strategies to induce cell-mediated and humoral immunity against HIV.
AIDS Res Hum Retroviruses, 14 (1998), pp. S8-S291
[119.]
T. Hanke, R.V. Samuel, T.J. Blanchard, V.C. Neumann, T.M. Allen, J.E. Boyson, et al.
Effective induction of simian immunodeficiency virus-specific cytotoxic T lymphocytes in macaques by using a multiepitope gene and DNA prime-modified vaccinia virus ankara boost vaccination regimen.
J Virol, 73 (1999), pp. 7524-7532
[120.]
A. Seth, I. Ourmanov, J.E. Schmitz, M.J. Kuroda, M.A. Lifton, C.E. Nickerson, L. Wyatt, et al.
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, 74 (2000), pp. 2502-2509
[121.]
J.W. Shiver, T.M. Fu, L. Chen, D.R. Casimiro, M.E. Davis, R.K. Evans, et al.
Replication-incompetent adenoviral vaccine vector elicits effective anti-immunodeficiency-virus immunity.
Nature, 415 (2002), pp. 331-335
[122.]
D. Trono.
Lentiviral vectors: Turning a deadly foe into a therapeutic agent.
Gene Ther, 7 (2000), pp. 20-23
[123.]
N.L. Davis, I.J. Caley, K.W. Brown, M.R. Bett, D.M. Irlbeck, K.M. McGrath, et al.
Vaccination of macaques against pathogenic simian immunodeficiency virus with Venezuelan equine encephalitis virus replicon particles.
J Virol, 74 (2000), pp. 371-378
[124.]
X. Chen, G. Scala, I. Quinto, W. Liu, T.W. Chun, J. Shaw, et al.
Protection of rhesus macaques against disease progression from pathogenic SHIV-89.6PD by vaccination with phage-displayed HIV-1 epitopes.
Nature Med, 7 (2001), pp. 1225-1231
[125.]
M. Kameoka, Y. Nishino, K. Matsuo, N. Ohara, T. Kimura, A. Yamazaki, et al.
T lymphocyte response in mice induced by a recombinant BCG vaccination which produces an extracellular alpha antigen that fused with the human immunodeficiency virus type 1 envelope immun-odominant domain in the V3 loop.
Vaccine, 12 (1994), pp. 153-158
[126.]
M. Honda, K. Matsuo, T. Nakasone, Y. Okamoto, H. Yoshizaki, K. Kitamura, et al.
Protective immune responses induced by secretion of a chimeric soluble protein from a recombinant Mycobacterium bovis bacillus Calmette-Guérin vector candidate vaccine for human immun-odeficiency virus type 1 in small animals.
Proc Natl Acad Sci USA, 92 (1995), pp. 10693-10697
[127.]
J.D. Boyer, J. Kim, K.l. Ugen.
HIV-1 DNA vaccines and chemokines.
Vaccine, 17 (1999), pp. S40-S536
[128.]
J.D. Boyer, A.D. Cohen, S. Vogt.
Vaccination of seronegative volunteers with a human immunodeficiency virus type 1 env/rev DNA vaccine induces antigen-specific proliferation and lymphocyte production of _-chemokines.
J Infect Dis, 181 (2000), pp. 476-483
[129.]
D.H. Barouch, S. Santra, J. Schmitz, A. Kuroda.
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 USA, 97 (2000), pp. 4192-4197
[130.]
D.H. Barouch, S. Santra, J. Schmitz, A. Kuroda, T.M. Fu, W. Wagner, et al.
Control of viremia and prevention of clinical AIDS in rhesus monkeys by cytokine-augmented DNA vaccination.
Science, 290 (2000), pp. 486-492
[131.]
D.H. Barouch, S. Santra, J. Schmitz, A. Kuroda, T.M. Fu, W. Wagner, et al.
Control of viremia and prevention of clinical AIDS in rhesus monkeys by cytokine-augmented DNA vaccination.
Science, 290 (2000), pp. 486-492
[132.]
J.C. Cox, A.R. Coulter.
Adjuvants a classification and a review of their modes of action.
Vaccine, 15 (1997), pp. 248-256
[133.]
T. Hanke, A. McMichael.
Pre-clinical development of a multi-CTL epitopebased DNA prime MVA boost vaccine for AIDS.
Immunol Lett, 66 (1999), pp. 177-181
[134.]
McMichael A. DNA/MVA prime boost for an A clade vaccine. XIV International AIDS Conference. Barcelona, Spain, July 2002 [Abstract n.° 208]
[135.]
J. Salk.
Prospects for the control of AIDS by immunizing seropositive individuals.
Nature, 327 (1987), pp. 473-476
[136.]
R. Hoff, J. McNamara.
Therapeutic vaccines for preventing AIDS: Their use with HAART.
Lancet, 353 (1990), pp. 1723-1724
[137.]
E. Sandström, B. Wahren.
Therapeutic immunisation with recombinant gp160 in HIV-1 infection: A randomised double-blind placebo-controlled trial. Nordic VAC-04 Study Group.
Lancet, 353 (1999), pp. 1735-1742
[138.]
F.D. Goebel, J.W. Mannhalter, R.B. Belshe.
Recombinant gp160 as a therapeutic vaccine for HIV-infection: Results of a large randomized, controlled trial.
AIDS, 13 (1999), pp. 1461-1468
[139.]
D.L. Birx, L.D. Loomis-Price, N. Aronson.
Efficacy testing of recombinant human immunodeficiency virus (HIV) gp160 as a therapeutic vaccine in early-stage HIV-1-infected volunteers.
J Infect Dis, 181 (2000), pp. 881-889
[140.]
A.M. Levine, S. Groshen, J. Allen.
Initial studies on active immunization of HIV-1 infected subjects using a gp120-depleted HIV-1 immunogen: Long-term follow-up.
J Acquir Immune Defic Syndr Hum Retrovirol, 11 (1996), pp. 351-364
[141.]
R.B. Moss, F. Ferre, A. Levine.
Viral load, CD4 percentage, and delayed-type hypersensitivity in subjects receiving the HIV-1 immunogen and antiviral drug therapy.
J Clin Immunol, 16 (1996), pp. 266-271
[142.]
J.O. Kahn, D.B. Cherng, K. Mayer, H. Murray, S. Lagakos.
The 806 Investigator team. Evaluation of HIV-1 Immunogen, an Immunologic Modifier, Administered to Patients Infected Whith HIV Having 300 to 549 × 106/L CD4 counts.
Jama, 284 (2000), pp. 2193-2202
[143.]
Diaz L, Podzamczer D, Canto-Nogues C, Rodriguez-Sainz MC, Carbone S, Moreno S, et al. 3-year evaluation of a therapeutic vaccine (HIV-1 immunogen) administred with antiretrovirals versus antiretroviral therapy alone in patients with HIV chronic infection. XIV International AIDS Conference. Barcelona, Spain, July 2002 [Abstract n.– 1482].
[144.]
Robinson H. Working towards an AIDS Vaccine. XIV International AIDS Conference. Barcelona, Spain, July 2002 [Abstract n.° 212]
[145.]
Corey L. HIV preventive vaccines: Science and politics. XIV International AIDS Conference. Barcelona, Spain, July 2002 [Abstract n.° 143]
[146.]
R.M. Anderson, G.P. Garnett.
Low-efficacy HIV vaccines: Potential for community-based intervention programmes.
Lancet, 348 (1996), pp. 1010-1013
[147.]
S.H. Vermund.
Rationale for the testing and use of a partially effective HIV vaccine.
AIDS Res Hum Retroviruses, 14 (1998), pp. S321-S323
[148.]
Anderson R. Impact of a partially effective vaccine. XIV International AIDS Conference. Barcelona, Spain, July 2002 [Abstract n.° 133]
[149.]
G. Ferrari, W. Humphrey, M.J. McElrath.
Clade B-based HIV-1 vaccines elicit cross-clade cytotoxic T lymphocyte reactivities in uninfected volunteers.
Proc Natl Acad Sci USA, 94 (1997), pp. 396-401
[150.]
F. Verrier, S. Burda, R. Belshe, Am. Duliege, J.L. Excler, M. Klein, et al.
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, 74 (2000), pp. 10025-10033
[151.]
R.A. LaCasse, K.E. Follis, M. Trahey, J.D. Scarborough, D.R. Littman, J.H. Nunberg.
Fusion-competent vaccines: Broad neutralization of primary isolates of HIV.
Science, 283 (1999), pp. 357-362
[152.]
Emini E. An HIV-1 Vaccine using a replication-defective adenoviral vector. XIV International AIDS Conference. Barcelona, Spain, July 2002 [Abstract n.° 210]
[153.]
Suraratdecha C, Ainswort M, Tangcharoensathien V. The demand for an HIV/AIDS vaccine among high-risk groups: Does risk matter? XIV International AIDS Conference. Barcelona, Spain, July 2002 [Abstract n.° 1301]
[154.]
UNAIDS. AIDS vaccine research in Asia: Needs and opportunities. Report from a UNAIDS/WHO/NIID meeting, Tokyo, 1998.
AIDS, 13 (1999), pp. 1-13
[155.]
R.T. Mahoney, J.E. Maynard.
The introduction of new vaccines into developing countries.
Vaccine, 17 (1999), pp. 646-652
[156.]
B.R. Bloom.
The highest attainable standard: Ethical issues in AIDS vaccines.
Science, 279 (1998), pp. 186-188
[157.]
D. Guenter, J. Esparza, R. Macklin.
Ethical considerations in international HIV vaccine trials: Summary of a consultative process conducted by the Joint United Nations Programme on HIV/AIDS (UNAIDS.
J Med Ethics, 26 (2000), pp. 37-43
[158.]
UNAIDS. Ethical considerations in HIV preventive vaccine research (document UNAIDS/00.07E.
WHO, (2000),
[159.]
Isbell MT, Widdus R, Williams L, Gold D. Minimizing Regulatory Delays in the Approval and Licensure of New HIV/AIDS Vaccines. XIV International AIDS Conference. Barcelona, Spain, July 2002 [Abstract n.° 1302]
[160.]
M.C. Boily, B.R. Masse, K. Desai, M. Alary, R.M. Anderson.
Some important issues in the planning of phase III HIV vaccine efficacy trials.
Vaccine, 17 (1999), pp. 989-1004
[161.]
M.R. Hilleman.
The business of science and the science of business in the quest for an AIDS vaccine.
Vaccine, 17 (1999), pp. 121-122
Copyright © 2002. Elsevier España, S.L.. Todos los derechos reservados
