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Protection Against Late-Onset AIDS in Macaques Prophylactically Immunized with a Live Simian HIV Vaccine Was Dependent on Persistence of the Vaccine Virus¹

Glenn A. Mackay^*,,, Zhenqian Liu^*, Dinesh K. Singh^*,, Marilyn S. Smith, Sampa Mukherjee^*, Darlene Sheffer^*, Fenglan Jia^*, Istvan Adany^*, Kelvin H. Sun^*, Sukhbir Dhillon^*, Wu Zhuge^* and Opendra Narayan^2,*,

^* Marion Merrell Dow Laboratory of Viral Pathogenesis, Division of Infectious Diseases, Department of Medicine, and Department of Microbiology, Molecular Genetics, and Immunology, University of Kansas Medical Center, Kansas City, KS 66160

This is a 5-year follow-up study on 12 macaques that were immunized orally with two live SHIV vaccines, six with V1 and six with V2. All 12 macaques became persistently infected after transient replication of the vaccine viruses; all were challenged vaginally 6 mo later with homologous pathogenic SHIV_KU-1. Two of the V1 group developed full-blown AIDS without evidence of vaccine virus DNA in tissues. The data on the 10 vaccinated survivors showed that all 10 became infected with SHIV_KU-1 and that DNA of both vaccine and SHIV_KU-1 viruses were present 6 mo postchallenge, with minimal replication of SHIV_KU-1. During the following 5 years, these animals remained persistently infected, but with only one of the two viruses. Six animals eliminated their vaccine virus after variable periods of time and four of these succumbed to reactivation of the challenge virus and AIDS. Five years after challenge, four latently infected animals, two with V2 and two with SHIV_KU-1, were reinoculated with SHIV_KU-1. This resulted in transient superinfection and the animals promptly returned to their prechallenge status. Immunosuppression of the four animals 1 year later with Abs to CD8⁺ lymphocytes resulted in transiently productive replication of their respective latent viruses, and upon recovery of CD8⁺ lymphocytes, they reverted to their latent virus status. The major finding was that of eight animals that eliminated the vaccine virus, six developed AIDS. The two others harboring SHIV_KU-1 remain at risk for developing late-onset disease. The primary correlate against AIDS was persistence of the vaccine virus.

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