AEGiS-11IAC: Immune responses in cynomolgus macaques infected with pathogenic or attenuated SIV.

11th International AIDS Conference

Vancouver, British Columbia — July 7-12, 1996

Immune responses in cynomolgus macaques infected with pathogenic or attenuated SIV.

Int Conf AIDS 1996 Jul 7-12; 11:4 (abstract no. Mo.A.104)
Rud EW, Sheering A, Bogdanovic D, Ko D, Vogel T, Cook N, Hall G, Cranage MP, Parenteau M, Beausoleil N, Fournier J; Health Canada, LCDC, National Laboratory for HIV Pathogenesis, Ottawa, Ontario, Canada. Fax: 613-957-7238. E-mail: erud@hpb.hwc.ca.

OBJECTIVE: To determine the immune responses induced by infection of macaques with either an attenuated or pathogenic variant of SIVmac32H and ultimately to correlate these to the protection induced against subsequent heterologous challenge with virus derived from SIVsmm.

METHODS: Three groups of 8 cynomolgus macaques were infected with virus derived from SIVmac32H(pJ5), SIVmac32H(pC8) or mock infected. The C8 molecular clone is a naturally attenuated variant containing a 12 bp deletion in the nef/3'LTR region. To determine the breadth of this protection we will challenge these macaques with virus derived from SIVsmm(pBJ14). The virus load in these infected macaques was determined by limiting dilution of PBMCs and cocultivation with C8166 cells. CD4/CD8 analysis was performed by flow cytometry. Proviral DNA and viral RNA loads in circulating PMBCs and plasma were determined by limiting dilution of PBMC DNA and nested set PCR and bDNA analysis of plasma associated RNA. Isolated PBMCs were used in the following immunological studies: CTLp frequencies to various SIV proteins; the TCR repertoire; cytokine pattern of expression; lymphocyte proliferation to PWM, cynomolgus EBV and SIVmac gp120 and Mixed lymphocyte Reactions (MLRs). The macaques were also followed by hematology, blood biochemistry and weight gain.

RESULTS: Two weeks post inoculation the macaques infected with C8 had a lower virus load then those infected with J5. The virus load decreased much quicker in C8 infected macaques. The macaques responded similarly to PWM, cynomolgus EBV and in MLRs and the SIV infected macaques responded similarly to SIVmac gp120. The Vbeta repertoire of the TCR, in general, showed no selection for a specific subtype of Vbeta expression. The CD4/CD8 ratios did not vary over normal biological variation. The CTLp frequencies to SIVmac gp160 and SIVmac RT, the antibody titres directed against SIVmac gp120, and the cytokine profiles are all being examined at present.

CONCLUSIONS: The immune responses in macaques infected with either the attenuated or non-attenuated variants of SIVmac32H do not seem to differ. It seems that the macaques are able to control the C8 infection by an immune response which is not as active against the J5 virus. This immune response will be under further investigation.

Keywords: AEGIS, SIV, Macaca, Macaca mulatta, Macaca fascicularis, Viral Load, Immunity, Polymerase Chain Reaction, Vaccination, DNA Primers, Antigens, CD8, Cytokines, Animal, immunology, ICA11

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MoA104