INFECTED MACAQUES THAT CONTROLLED REPLICATION OF SIVMAC OR NONPATHOGENIC SHIV DEVELOPED STERILIZING RESISTANCE AGAINST PATHOGENIC SHIVKU-1

Twenty macaques were used to evaluate the ability of nonpathogenic SIV mac or nonpathogenic chimeric SIV-HIV (SHIV) to induce protection in m acaques against superinfection with a pathogenic variant of SHIV (SHIV KU-1) originally containing the rat, rev, vpu, and env of HIV-I (strai n HXB2) in a genetic background of SIV(mac)239, Specifically, three ma caques inoculated with molecularly cloned, macrophage-tropic SIV(mac)L G1 developed an early systemic infection but recovered with only trace s of SIVmac DNA in visceral lymphoid tissues. These animals were then inoculated parenterally with pathogenic SHIVKU-1. All three animals re sisted infection with SHIVKU-1, as indicated by lack of virus recovery and absence of SHIV-specific env and vpu sequences in the visceral ly mphoid tissues and multiple regions in the CNS. We also examined the a bility of five macaques that had been inoculated with nonpathogenic SH IV (NP-SHIV) to withstand challenge with the pathogenic SHIVKU-1. Like the SIV(mac)LG1-inoculated macaques, these animals also resisted SHIV KU-1 challenge as judged by the inability to recover infectious virus, normal CD4(+) T cell counts, and the absence of SHIVKU-1 signature se quences in the lymph node tissue. Thus, eight of eight animals that de veloped control over primary lentivirus infections had also developed resistance to infection with pathogenic SHIVKU-1. Three groups of maca ques were used as controls for this study. The first group consisted o f six macaques inoculated with SHIVKU-1 alone. All animals developed v iremia, showed severe loss of CD4(+) T cells within 4 weeks, and succu mbed to AIDS within 6 months. The second group of three macaques was i noculated first with SHIVKU-1 and inoculated later with uncloned, neur ovirulent SIV(mac)7F-Lu. A third group of three macaques was inoculate d with SIV(mac)7F-Lu followed by inoculation with SHIVKU-1. PCR analys es using oligonucleotide primers specific for the SIV or HIV env revea led that macaques from the last two groups had widespread infection wi th both SHIVKU-1 and SIVmac indicating that animals that failed to con trol productive replication of either SHIVKU-1 or SIV(mac)7F-Lu could not resist superinfection with the other virus. These data indicate th at sterilizing immunity against the virulent SHIV could be induced in animals that had experienced an immunizing infection. Moreover, the di vergence of the envelope glycoprotein of the protective avirulent and virulent challenge virus suggests that a single vaccine could protect against infection with a virus containing a different envelope glycopr otein. (C) 1997 Academic Press.