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

• Published in: The Journal of immunology (1950) 2004-09, Vol.173 (6), p.4100-4107
• Main Authors: Mackay, Glenn A, Liu, Zhenqian, Singh, Dinesh K, Smith, Marilyn S, Mukherjee, Sampa, Sheffer, Darlene, Jia, Fenglan, Adany, Istvan, Sun, Kelvin H, Dhillon, Sukhbir, Zhuge, Wu, Narayan, Opendra
• Format: Article
• Language: English
• Subjects: Administration, Oral; Animals; CD8-Positive T-Lymphocytes; Female; Follow-Up Studies; Immunity, Cellular; Immunization Schedule; Immunization, Secondary; Lymphocyte Depletion - methods; Macaca nemestrina; RNA, Viral - blood; SAIDS Vaccines - immunology; SAIDS Vaccines - therapeutic use; Simian Acquired Immunodeficiency Syndrome - immunology; Simian Acquired Immunodeficiency Syndrome - mortality; Simian Acquired Immunodeficiency Syndrome - prevention & control; Simian Acquired Immunodeficiency Syndrome - virology; Simian Immunodeficiency Virus - immunology; Simian/human immunodeficiency virus; Vaccines, Attenuated - immunology; Vaccines, Attenuated - therapeutic use; Virus Activation - immunology; Virus Latency - immunology; Virus Replication - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.173.6.4100

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.