PROTECTION OF MONKEYS BY A SPLIT VACCINE AGAINST SIV(MAC) DEPENDS UPON BIOLOGICAL PROPERTIES OF THE CHALLENGE VIRUS

Objective: To investigate the role of the anti-cellular immune response in the protection of rhesus macaques against infection with the simian immunodeficiency virus SIV(mac). 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 SIV(mac) split vaccine was administered to rhesus macaques and their anti-, B- and T-cell response monitored. Vaccinees and controls were challenged with SIV(mac) 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 SIV(mac251)/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 SIV(mac251) (SIV(mac251)/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 SIV(mac251)/32H or SIV(mac251)/MPBMC did not correlate with anti-cellular antibodies or proliferative T-cell reactivities. Control animals infected with SIV(mac251)/MPBMC showed high persistent antigenaemia and high plasma virus titres. Both were absent in controls infected with complement C8166-grown SIV(mac251)/32H. Whereas the latter always seroconverted against the full panel of viral polypeptides, SIV(mac251)/MPBMC-infected animals showed a drastically decreased antibody response. Conclusions: Neither the antibody nor the proliferative T-cell response to SIV(mac) correlates with protection from virus challenge. In contrast to SIV(mac251)/32H grown on C8166 cells, the MPBMC-grown challenge virus SIV(mac251) appears to belong to the 'rapid-high' phenotype, possibly explaining the lack of protection against this SIV.