Objective To investigate the role of the anti-cellular immune response in the protection of rhesus macaques against infection with the simian immunodeficiency virus SIVmac. To determine the biological differences between SIV challenge stocks grown either on human T-cell lines or on monkey peripheral blood mononuclear cells (MPBMC). Design A protective SIVmac split vaccine was administered to rhesus macaques and their anti-, B- and T-cell response monitored. Vaccinees and controls were challenged with SIVmac grown either on human or on monkey cells. The in vivo replication rate of, and the immune response to, the two viruses was compared. Methods Five rhesus macaques were immunized with a total of 2 mg each of purified SIVmac251/32H grown on the human C8166 T-cell line. The antibody and proliferative T-cell responses were evaluated by enzyme-linked immunosorbent assay and T-cell proliferation assay, respectively. Four protected animals and four controls were reboosted and challenged with MPBMC-grown SIVmac251 (SIVmac251/MPBMC). Cell-free virus load was determined by titration of plasma for SIV infectivity on C8166 cells and antigen with a core antigen capture assay. Results Protection from virus challenge with C8166-grown SIVmac251/32H or SIVmac251/ MPBMC did not correlate with anti-cellular antibodies or proliferative T-cell reactivities. Control animals infected with SIVmac251/MPBMC showed high persistent antigenaemia and high plasma virus titres. Both were absent in controls infected with complement C8166-grown SIVmac251/32H. Whereas the latter always seroconverted against the full panel of viral polypeptides, SIVmac251/MPBMC-infected animals showed a drastically decreased antibody response. Conclusions Neither the antibody nor the proliferative T-cell response to SIVmac correlates with protection from virus challenge. In contrast to SIVmac251/32H grown on C8166 cells, the MPBMC-grown challenge virus SIVmac251 appears to belong to the 'rapid-high' phenotype, possibly explaining the lack of protection against this SIV.
Vaccines prepared from purified viral envelope complexes are effective against certain animal model tumors induced by exogenous retroviruses. Related viruses have recently been isolated from humans and obviously cause adult T-cell leukemia and the acquired immunodeficiency syndrome. Knowledge accumulated in experiments with subunit vaccines against animal retroviruses could help to develop immunopreventive regimens against human retroviruses.
Abstract A glycoprotein of an apparent molecular mass of 46000, gp 46, was enriched by affinity chromatography from the virus-and cell-free culture medium of adult T-cell leukemia virus (ATLV) infected cells, gp 46 was specifically precipitated with sera from patients with adult T-cell leukemia known to react with the adult T-cell leukemia associated antigen (ATLA). Thus, gp 46 is a novel component of the ATLA antigen complex.
Five monoclonal antibodies (mabs) specific for the envelope proteins of a simian immunodeficiency virus of African green monkeys (SIV agm ) have been raised. Two mabs were directed against distinct epitopes on the transmembrane protein gp41. A conformational epitope on the gp130 was recognized by three mabs. This is the first report on mabs specific for SIV agm‐gp130 . Studies of the cross‐reactivities revealed that the epitopes recognized by the env‐directed mabs are conserved species‐specifically in SIV agm isolates. Therefore, these mabs can be used to distinguish SIV agm strains from other virus groups.
The cellular immune response of seven rhesus macaques immunized with Tween-ether-treated macaque strain of simian immunodeficiency virus (SIVMAC) and three non-vaccinated control animals was investigated. Immunization elicited antigen-specific proliferating CD4+ cells in five of seven monkeys. Proliferating T cells were found in all animals protected from a first virus challenge. Cytotoxic T lymphocytes (CTLs) were not induced by the immunization. After the second challenge, the four formerly protected animals became infected, despite a strong proliferative CD4+ cell activity in three of them. All animals lost their proliferative activity 2 weeks after infection. After the first challenge four of the six infected animals exhibited a CTL response and after the second challenge, one of four newly infected macaques acquired a CTL response. The five animals with a CTL activity against SIVMAC proteins were protected from severe thrombocytopenia, which appeared in the five CTL-negative animals after infection. Our data show the induction of proliferative T cells by immunization with soluble SIVMAC antigen. This T cell reactivity was found in all animals protected from the first virus challenge, but did not confer protection from the second challenge. Interestingly, the proliferative T cell reactivity disappeared 2 weeks after virus infection. Furthermore a CTL response against viral proteins seems to protect infected animals from severe thrombocytopenia which is an early sign of AIDS in monkeys.
