However, we observed considerable variation in the levels of SIVmac239nef replication among the immunized animals (notably 1484 and 1490), with almost a 2-log range in peak ideals between different animals
However, we observed considerable variation in the levels of SIVmac239nef replication among the immunized animals (notably 1484 and 1490), with almost a 2-log range in peak ideals between different animals. of four challenged at 10 weeks, in none of four challenged at 15 weeks, and one of four challenged at 25 weeks. One animal immunized with SIVmac239nef and challenged at 10 weeks experienced evidence of disease progression in the absence of detectable SIVmac251. Although total safety was not accomplished at 5 weeks, a transient reduction in viremia (approximately 100-collapse) occurred in the immunized macaques early after challenge compared to the nonimmunized settings. Two weeks after challenge, SIV RNA was also reduced in the lymph nodes of all immunized macaques compared with control animals. Taken together, these results indicate that sponsor reactions capable of reducing the viral weight in plasma and lymph nodes were induced as early as 5 Levamlodipine besylate weeks after immunization with SIVmac239nef, while more potent safety developed between 10 and 15 weeks. In further experiments, we found that resistance to SIVmac251 illness did not correlate with the presence of antibodies to SIV gp130 and p27 antigens and was accomplished in the absence of significant neutralizing activity against the primary SIVmac251 challenge stock. Immunization with live, attenuated strains of simian immunodeficiency disease (SIV) can induce safety against illness with virulent disease (2, 8, 10, 21, 22, 26, 31, 33). Despite these motivating results, safety issues persist on the possible use of live, attenuated HIV vaccines in humans (3). As a result, research attempts by several groups have focused on elucidating the underlying mechanisms associated with protecting immunity with this model. Although several studies have evaluated the humoral (1, 6, 12, 22, 24, 26, 33) and cellular (13, 16) immune reactions in monkeys immunized with live, attenuated SIV, the correlates of protecting immunity remain unclear. Initial studies suggested that maturation of the protecting response took a prolonged period of time to develop, raising questions as to the nature of the induced immunity (8, 33). While immune reactions to SIV develop within a few weeks following illness with pathogenic strains (28, 34), safety was achieved only after 35 weeks Levamlodipine besylate following immunization of macaques with an attenuated macrophagetropic disease (SIV17E-Cl) (8) and 79 weeks after immunization having a triple-deletion mutant (SIV3) (33). In several studies, inoculation of macaques with highly attenuated strains of SIV, which were unable to set up persistent illness in the Levamlodipine besylate sponsor, failed to confer significant safety against difficulties by pathogenic viruses (11, 21). Taken together, these results suggest that the degree of attenuation of the vaccine strain and its ability to replicate in vivo are essential determinants of the protecting effect. Because sensitive, quantitative methods to measure SIV in plasma have only recently been formulated, detailed information within the replication kinetics of live, attenuated SIV in macaques is limited (12). To address this issue, we examined the replication of an attenuated strain of SIV (SIVmac239nef) in rhesus macaques by measuring plasma viremia via a quantitative branched DNA (bDNA) assay (9). Plasma viral weight was measured regularly following inoculation with SIVmac239nef and again after challenge with uncloned SIVmac251. To determine the temporal relationship between replication of the vaccine disease and the onset of safety, animals infected with SIVmac239nef were challenged with SIVmac251 at Levamlodipine besylate either 5, BIRC3 10, 15, or 25 weeks after immunization. Data on viral weight in the plasma and lymph nodes, as well as within the induction of anti-SIV antibody reactions, were then compared with end result following challenge. MATERIALS AND METHODS Macaques. Twenty adult, female rhesus macaques (for 60 min at 4C) and recognized by using probes that hybridize within the region of SIVmac. SIV RNA was quantified by comparison to.