Pathogenic simian/human immunodeficiency virus SHIVKU inoculated into immunized macaques caused infection, but virus burdens progressively declined with time

Using the simian immunodeficiency virus/human immunodeficiency virus (SHIV) -macaque model of AIDS, we had shown in a previous report that a live, nonp athogenic strain of SHIV,further attenuated by deletion of the vpu gene and inoculated orally into adult macaques, had effectively prevented AIDS foll owing vaginal inoculation with pathogenic SHIVKU. Examination of lymph node s from the animals at 18 weeks postchallenge had shown that all six animals were persistently infected with challenge virus. We report here on a 2-yea r follow-up study on the nature of the persistent infections in these anima ls. DNA of the vaccine virus was present in the lymph nodes at all time poi nts tested, as far as 135 weeks postchallenge. In contrast, the DNA of SHIV KU became undetectable in one animal by week 55 and in three others by week 63. These four macaques have remained negative for SHIVKU DNA as far as th e last time point examined at week 135. Quantification of the total viral D NA concentration in lymph nodes during the observation period showed a stea dy decline. All animals developed neutralizing antibody and cytotoxic-T-lym phocyte responses to SHIVKU that persisted throughout the observation perio d. Vaccine-like viruses were isolated from two animals, and a SHIVKU-like v irus was isolated from one of the two macaques that remained positive for S HIVKU DNA. There was no evidence of recombination between the vaccine and t he challenge viruses. Thus, immunization with the live vaccine not only pre vented disease but also contributed to the steady decline in the virus burd ens in the animals.