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

A substantial risk in using live attenuated, multiply deleted viruses as va ccines against AIDS is their potential to induce AIDS. A mutant of the simi an immunodeficiency virus (SIV) with large deletions in nef and vpr and in the negative regulatory element induced AIDS in six of eight infant macaque s vaccinated orally or intravenously. Early signs of immune dysfunction wer e seen in the remaining two offspring. Prolonged follow-up of sixteen vacci nated adult macaques also showed resurgence of chronic viremia in four anim als: 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.