Kato, M. post-infection on primary viral replication in a macaque AIDS model. Methods and Findings The inoculums for passive immunization with simian immunodeficiency computer virus mac239 (SIVmac239)-specific neutralizing activity were prepared by purifying polyclonal immunoglobulin G from pooled plasma of six SIVmac239-infected rhesus macaques with NAb induction in the chronic phase. Passive immunization of rhesus macaques with the NAbs at day 7 after SIVmac239 challenge resulted in significant reduction of set-point plasma viral loads and preservation of central memory CD4 T lymphocyte counts, despite the limited detection period of the administered NAb responses. Peripheral lymph node dendritic cell (DC)-associated viral RNA loads showed a remarkable peak with the NAb administration, and DCs stimulated in vitro with NAb-preincubated SIV activated virus-specific CD4 T lymphocytes in an Fc-dependent manner, implying antibody-mediated virion uptake by DCs and enhanced Fosfructose trisodium T cell priming. Conclusions Our results present evidence indicating that potent antibody induction post-infection can result in primary immunodeficiency computer virus control and suggest direct and indirect contribution of its absence to initial control failure in HIV infections. Although difficulty in achieving requisite neutralizing titers for sterile HIV protection by prophylactic vaccination has been suggested, this study points out a possibility of non-sterile HIV control by prophylactic vaccine-induced, sub-sterile titers of NAbs post-infection, providing a rationale of vaccine-based NAb induction for primary HIV control. Introduction In the natural courses of HIV infections, the host Fosfructose trisodium immune responses fail to contain the computer virus replication and allow persistent plasma viremia. While virus-specific cytotoxic T lymphocyte (CTL) responses exert strong suppressive pressure on primary HIV replication [1]C[7], the contribution of virus-specific antibodies in clearance of primary HIV contamination has remained unclear [8]. Neutralizing antibodies (NAbs) play a central role in control of most viral infections, but in HIV infections, NAb induction is not efficient in the early phase Akap7 due to its unusual neutralization-resistant nature, such as the sophisticated masking of neutralizing epitopes in HIV envelope [8]C[11], and protective efficacies of post-infection NAbs in vivo have remained elusive. While evidence of computer virus escape implies NAb selective pressure to a certain extent [10], [12]C[13], it has been speculated that post-infection NAbs could exert only a limited suppressive effect on primary HIV replication [14]C[16]. Post-infection passive NAb immunization studies in macaque AIDS models would contribute to elucidation of its protective role, in complementation with studies determining the requisites for sterile protection by pre-challenge administered NAb titers [14], [16]C[21]. A model of CCR5-tropic simian immunodeficiency computer virus (SIV) contamination that induces acute loss of memory CD4+ T cells like HIV infections in humans [22]C[25] would be adequate for assessment of post-infection NAb efficacies in primary immunodeficiency computer virus contamination. In the present study, we examined the effect of passive NAb immunization at day 7 post-challenge on primary viral replication in a macaque Fosfructose trisodium AIDS model Fosfructose trisodium of CCR5-tropic SIVmac239 contamination. Remarkably, our analysis revealed control of primary SIVmac239 replication by the passive NAb immunization post-infection. Methods Animal experiments Burmese rhesus macaques (NAb responses past then. In the naive controls, no SIVmac239-specific NAbs were detected throughout the course. This discrepancy between the transient NAb detection and the persistent viremia control in the NAb-immunized macaques differed from previously-reported, dose-dependent establishment of sterile protection from CXCR4-tropic SHIV contamination by pre-challenge passive NAb immunization [18]C[21]. Difference in total CD4+ T-cell counts was not found throughout the course between the two groups (Physique 2A). Reductions in peripheral CD95+ CD28+ central memory CD4+ T-cell counts [28]C[29] were observed in the naive controls after SIV challenge (Physique 2B). The NAb-immunized macaques, however, showed significantly higher central memory CD4+ T-cell counts around 3 months post-challenge than those in the naive controls (and 90-120-Ia, respectively (Physique 4A). In the former group of macaques possessing 90-088-Ij, vaccinees failed to control SIV replication even after passive NAb immunization (Physique 4B). In the latter group of macaques possessing 90-120-Ia, all 4 vaccinees without NAb immunization controlled SIVmac239 replication and had undetectable plasma viral loads after week 8 post-challenge (Physique 4B). All of them rapidly selected for a mutation escaping from Gag206-216 epitope-specific CTL by week 5, suggesting a strong selective pressure on the computer Fosfructose trisodium virus by this CTL [6]. As for the two vaccinees VA2 and VA3 infused with NAbs, plasma viremia became undetectable by week 5 and rapid selection of CTL escape mutation was not observed (data not shown). SIV-specific CD8+ T-cell frequencies at week 2 in the NAb-immunized.