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Pathogenicity of Live, Attenuated SIV After Mucosal Infection of Neonatal Macaques
Abstract
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 an 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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Cited by
Tet-On Systems For Doxycycline-inducible Gene Expression
T. Das, A., Tenenbaum, L., & Berkhout, B. (2016) · Current Gene Therapy · doi:10.2174/1566523216666160524144041 · Cited by 434
“Evolution of the vaccine virus to a pathogenic variant did indeed cause disease in a minority of the vaccinated animals [46-49].”
BackgroundBaba, T. W., Liska, V., Khimani, A. H., Ray, N. B., Dailey, P. J., Penninck, D., Bronson, R., Greene, M. F., McClure, H. M., Martin, L. N., et al. (1999) · Nature Medicine · doi:10.1038/5557 · Cited by 356
Self-citationControl of SHIV-89.6P-infection of cynomolgus monkeys by HIV-1 Tat protein vaccine
Cafaro, A., Caputo, A., Fracasso, C., Maggiorella, M. T., Goletti, D., Baroncelli, S., Pace, M., Sernicola, L., Koanga-Mogtomo, M. L., Betti, M., et al. (1999) · Nature Medicine · doi:10.1038/9488 · Cited by 276
Marzio, G., Verhoef, K., Vink, M., & Berkhout, B. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.111031498 · Cited by 81
van der Velden, Y. U., Kleibeuker, W., Harwig, A., Klaver, B., Siteur-van Rijnstra, E., Frankin, E., Berkhout, B., & Das, A. T. (2016) · Virology · doi:10.1016/j.virol.2015.11.004 · Cited by 3
Metadata
- Authors
- Baba, T. W., Jeong, Y. S., Pennick, D., Bronson, R., Greene, M. F., & Ruprecht, R. M.
- Venue
- Science
- Published
- 1995-03-24
- Volume
- 267
- Issue
- 5205
- Pages
- 1820-1825
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2009369926
- Cited by
- 489
- References
- 37
- FWCI
- 14.46
- Type
- journal article
- Language
- en
- Open access
- closed
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