The purpose of this grant is to test the immunogenicity and efficacy of an SIV envelope DNA vaccine in rhesus monkeys against IV challenge infection and induction of simian AIDS with virulent SIVmac. During the first year we carried out a study of four SIV infected macaques to compare standard assays of infectivity and immune response with newly developed nonhuman primate cytokine assays. We did this preliminary study because we felt it important to establish the pattern and validity of these tests, especially the cytokine assays, in SIV infected monkeys before attempting to alter the response to infection by genetic immunization. Each of the four SIVmac251 inoculated monkeys became readily infected as based on virus infectivity assays on plasma, PBM and lymph node. Virus was cleared readily from the plasma of three monkeys but one monkey had a persistently high virus load. This monkey failed to make an anti-SIV immune response and was euthanized at 20 weeks with clinical signs of simian AIDS. The other three monkeys remained healthy at 24 weeks at which time the experiment was terminated; two of these animals made the expected strong SIV antibody response. The most significant result was a dramatic increase in PBMC constitutive expression of IL6, IL10 and TNFa mRNAs in all four infected monkeys at 24 weeks but not in two uninfected controls. There was little or no constitutive expression of IL4 or IFN mRNAs in the infected animals at this time. These findings indicate that acute SIV infection is accompanied by a predominance of Th-2 cytokines that presumably favors humoral over cellular immune responses. Insofar as genetic immunization is supposed to predominantly stimulate cellular immune responses (via Th-1 cytokines) our preliminary cytokine analysis of infected monkeys will be very useful for comparison with immunized and challenged monkeys.
NIH ExPorter
NIH ExPorter