LIVE ATTENUATED SIV VACCINES ARE NOT EFFECTIVE IN A POSTEXPOSURE VACCINATION MODEL

Live attenuated sinian immunodeficiency virus (SIV) vaccines, like nef deletion mutants, have been the most effective vaccines tested in the SIV/macaque model so far, The efficacy of live attenuated SIV vaccine s in therapeutic vaccination and postexposure prophylaxis has not been determined. Inoculation of macaques with a pathogenic challenge virus and an attenuated SIV vaccine at the same time mimics postexposure va ccination, whereby vaccination with the attenuated virus is performed as rapidly as possible after exposure to pathogenic SIV, In the study presented here, four rhesus macaques were coinfected with pathogenic S IV and a nearly 3000-fold excess of a nef deletion mutant of SIV, Four macaques received pathogenic SIV and an approximately 200-fold excess of a nef deletion mutant expressing interleukin 2 (IL-2), The IL-2-ex pressing SIV had been previously constructed to enhance the immunogeni city of live attenuated SIV vaccines, All coinfected macaques had a hi gh viral load, and some of them developed AIDS-like symptoms and patho logical alterations rapidly. In the presence of pathogenic SIV, both l ive attenuated SIV vaccines did not protect from disease in this poste xposure vaccination model.