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Live attenuated, multiply deleted simian immunodeficiency virus causes AIDS in infant and adult macaques

An Erratum to this article was published on 01 May 1999

Abstract

A substantial risk in using live attenuated, multiply deleted viruses as vaccines against AIDS is their potential to induce AIDS. A mutant of the simian immunodeficiency virus (SIV) with large deletions in nef and vpr and in the negative regulatory element induced AIDS in six of eight infant macaques vaccinated orally or intravenously. Early signs of immune dysfunction were seen in the remaining two offspring. Prolonged follow–up of sixteen vaccinated adult macaques also showed resurgence of chronic viremia in four animals: two of these developed early signs of disease and one died of AIDS. We conclude that this multiply deleted SIV is pathogenic and that human AIDS vaccines built on similar prototypes may cause AIDS.

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Figure 1: PCR detection of additional deletions within the 3´ LTR/nef regions of genomic DNA isolated from SIVmac239Δ3–infected animals.
Figure 2: Kaplan–Meier survival curves for infants inoculated orally or intravenously as neonates with SIVmac239Δ3 (solid line) or orally with wild–type SIVmac251 (dotted line).
Figure 3: Western blot analysis of plasma samples obtained from SIVmac239Δ3–infected infant/mother pair (a–c) and adult N141 (d).
Figure 4: In situ hybridization analysis of lymph node sections from infant/mother pair 93–4/A95.

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Acknowledgements

We thank J. Andersen (Harvard School of Public Health) for assistance with statistical analyses, R. Desrosiers (New England Regional Primate Research Center) for his contribution of SIVmac239Δ3 virus stock, P. Mack for veterinary care, A. Li for help with western blot analysis, C. Lanclos for technical assistance, and C. Gallegos and S. Sharp for the preparation of this manuscript. Supported in part by NIH grants RO1–AI32330, UO1–AI24345, and RO1–AI35533 to R.M.R. and by the Center for AIDS Research core grant IP30 28691. T.W.B. is a recipient of an NIH Clinical Investigator Development Award (KO8–AI01327). Supported also in part by NIH/NCRR grants RR–00164 and RR–00165 awarded to the Tulane Regional Primate Research Center and to the Yerkes Regional Primate Research Center, respectively.

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Baba, T., Liska, V., Khimani, A. et al. Live attenuated, multiply deleted simian immunodeficiency virus causes AIDS in infant and adult macaques. Nat Med 5, 194–203 (1999). https://doi.org/10.1038/5557

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