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Science 24 March 1995:
Vol. 267. no. 5205, pp. 1820 - 1825
DOI: 10.1126/science.7892606
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Articles

Science, Vol 267, Issue 5205, 1820-1825
Copyright © 1995 by American Association for the Advancement of Science

articles

Pathogenicity of live, attenuated SIV after mucosal infection of neonatal macaques

TW Baba, YS Jeong, D Pennick, R Bronson, MF Greene, and RM Ruprecht

Department of Pediatrics, Tufts University School of Medicine, Boston, MA 02111.

Adult macaques do not develop disease after infection with a nef deletion mutant of the simian immunodeficiency virus (SIV) and are protected against challenge with pathogenic virus. This finding led to the proposal to use nef-deleted viruses as live, attenuated vaccines to prevent human acquired immunodeficiency syndrome (AIDS). In contrast, neonatal macaques developed persistently high levels of viremia after oral exposure to and SIV nef, vpr, and negative regulatory element (NRE) deletion mutant. Severe hemolytic anemia, thrombocytopenia, and CD4+ T cell depletion were observed, indicating that neither nef nor vpr determine pathogenicity in neonates. Because such constructs have retained their pathogenic potential, they should not be used as candidate live, attenuated virus vaccines against human AIDS.


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Strong Human Immunodeficiency Virus (HIV)-Specific Cytotoxic T-Lymphocyte Activity in Sydney Blood Bank Cohort Patients Infected with nef-Defective HIV Type 1.
W. B. Dyer, G. S. Ogg, M.-A. Demoitie, X. Jin, A. F. Geczy, S. L. Rowland-Jones, A. J. McMichael, D. F. Nixon, and J. S. Sullivan (1999)
J. Virol. 73, 436-443
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Enhanced T-Cell Immunogenicity and Protective Efficacy of a Human Immunodeficiency Virus Type 1 Vaccine Regimen Consisting of Consecutive Priming with DNA and Boosting with Recombinant Fowlpox Virus.
S. J. Kent, A. Zhao, S. J. Best, J. D. Chandler, D. B. Boyle, and I. A. Ramshaw (1998)
J. Virol. 72, 10180-10188
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Potential Contributions of Viral Envelope and Host Genetic Factors in a Human Immunodeficiency Virus Type 1-Infected Long-Term Survivor.
K. Grovit-Ferbas, J. Ferbas, V. Gudeman, S. Sadeghi, M. B. Goetz, J. V. Giorgi, I. S. Y. Chen, and W. A. O'Brien (1998)
J. Virol. 72, 8650-8658
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DNA Vaccination Affords Significant Protection against Feline Immunodeficiency Virus Infection without Inducing Detectable Antiviral Antibodies.
M. J. Hosie, J. N. Flynn, M. A. Rigby, C. Cannon, T. Dunsford, N. A. Mackay, D. Argyle, B. J. Willett, T. Miyazawa, D. E. Onions, et al. (1998)
J. Virol. 72, 7310-7319
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Temporal Analyses of Virus Replication, Immune Responses, and Efficacy in Rhesus Macaques Immunized with a Live, Attenuated Simian Immunodeficiency Virus Vaccine.
R. I. Connor, D. C. Montefiori, J. M. Binley, J. P. Moore, S. Bonhoeffer, A. Gettie, E. A. Fenamore, K. E. Sheridan, D. D. Ho, P. J. Dailey, et al. (1998)
J. Virol. 72, 7501-7509
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Identification of a Human Immunodeficiency Virus Type 2 (HIV-2) Encapsidation Determinant and Transduction of Nondividing Human Cells by HIV-2-Based Lentivirus Vectors.
E. Poeschla, J. Gilbert, X. Li, S. Huang, A. Ho, and F. Wong-Staal (1998)
J. Virol. 72, 6527-6536
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Role of the SH3-Ligand Domain of Simian Immunodeficiency Virus Nef in Interaction with Nef-Associated Kinase and Simian AIDS in Rhesus Macaques.
I. H. Khan, E. T. Sawai, E. Antonio, C. J. Weber, C. P. Mandell, P. Montbriand, and P. A. Luciw (1998)
J. Virol. 72, 5820-5830
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Progress in the Development of an HIV-1 Vaccine.
N. L. Letvin (1998)
Science 280, 1875-1880
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The Effect of Deletion of the V3 Loop of gp120 on Cytotoxic T Cell Responses and HIV gp120-Mediated Pathogenesis.
D. Kmieciak, T. J. Wasik, H. Teppler, J. Pientka, S. H. Hsu, H. Takahashi, K. Okumura, Y. Kaneko, and D. Kozbor (1998)
J. Immunol. 160, 5676-5683
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Recombinant Vaccine-Induced Protection against the Highly Pathogenic Simian Immunodeficiency Virus SIVmac251: Dependence on Route of Challenge Exposure.
J. Benson, C. Chougnet, M. Robert-Guroff, D. Montefiori, P. Markham, G. Shearer, R. C. Gallo, M. Cranage, E. Paoletti, K. Limbach, et al. (1998)
J. Virol. 72, 4170-4182
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Epithelial Uptake and Transport of Cell-Free Human Immunodeficiency Virus Type 1 and gp120-Coated Microparticles.
A. Kage, E. Shoolian, K. Rokos, M. Ozel, R. Nuck, W. Reutter, E. Kottgen, and G. Pauli (1998)
J. Virol. 72, 4231-4236
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Lysis of HIV-1-infected cells and inhibition of viral replication by universal receptor T cells.
O. O. Yang, A.-C. Tran, S. A. Kalams, R. P. Johnson, M. R. Roberts, and B. D. Walker (1997)
PNAS 94, 11478-11483
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Vaccine effect using a live attenuated nef-deficient simian immunodeficiency virus of African green monkeys in the absence of detectable vaccine virus replication in vivo.
B. Beer, M. Baier, J. zur Megede, S. Norley, and R. Kurth (1997)
PNAS 94, 4062-4067
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Candidate AIDS Vaccines.
B. S. Graham and P. F. Wright (1995)
N. Engl. J. Med. 333, 1331-1339
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Long-Term Survivors of Human Immunodeficiency Virus Type 1 Infection.
B. Clotet, L. Ruiz, A. Ibanez, J. Whyte, L. M. Dunkle, N. R. Farid, D. D. Ho, Y. Cao, G. Pantaleo, and A. S. Fauci (1995)
N. Engl. J. Med. 332, 1646-1648
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Constitutively Dead, Conditionally Live HIV-1 Genomes. EX VIVO IMPLICATIONS FOR A LIVE VIRUS VACCINE.
S. M. Smith, M. Khoroshev, P. A. Marx, J. Orenstein, and K.-T. Jeang (2001)
J. Biol. Chem. 276, 32184-32190
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Recombinant rabies virus as potential live-viral vaccines for HIV-1.
M. J. Schnell, H. D. Foley, C. A. Siler, J. P. McGettigan, B. Dietzschold, and R. J. Pomerantz (2000)
PNAS 97, 3544-3549
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In vitro evolution of a highly replicating, doxycycline-dependent HIV for applications in vaccine studies.
G. Marzio, K. Verhoef, M. Vink, and B. Berkhout (2001)
PNAS 98, 6342-6347
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