Abstract:
We showed previously that immunization with HIV-1 envelope glycoprotein gp160 resulted in significantly enhanced immune responses and anti-HIV-1 neutralizing antibodies in mice and in humans primed with live recombinant vaccinia virus expressing the same antigen. In the present work, we aimed to determine, first, whether similar immune response against SIV could be elicited in macaques with the combined immunization approach, and second, whether the response generated would be protective against SIV infection. We constructed a recombinant vaccinia virus (v-SE5) expressing the envelope glycoprotein gp160 of SIVmne under the control of vaccinia virus 7.5K promoter. Cells infected with v-SE5 produced the precursor gp160 as well as the cleavage products gp120 and gp32. Four M. fascicularis were immunized twice (at 0 and 8 week) with 2x10(8) pfu of v-SE5 by skin scarification. All four animals showed strong lymphoproliferative response to SIVmne following immunization. Envelope-specific antibodies were also detected by whole-virus ELISA and by immunoblot analysis. However, no neutralizing antibodies were detected. At week 62 and 70, all four animals were immunized with 0.5 mg of partially purified gp160 produced in recombinant baculovirus infected insect cells. A significant increase (greater than 30-fold) in SIV-specific antibody titer was detected 2 weeks after the first gp160 immunization, indicating the long-lasting immune memory generated by v-SE5 immunizations. At week 72, all four animals generated anti-SIV neutralizing antibodies with titers ranging from 1:48 to 1:200. These results indicated that significant enhancement of immune responses could be generated in macaques by a combined immunization regimen similar to that currently used in clinical trials of candidate HIV-1 vaccines. Immunized macaques are being evaluated for their ability to resist SIV challenge infection.
Keywords: Animal Antibodies, Viral/*BIOSYNTHESIS Cloning, Molecular Gene Products, env/GENETICS/IMMUNOLOGY HIV Envelope Protein gp120/GENETICS/IMMUNOLOGY HIV-1/IMMUNOLOGY Immunization Lymphocyte Transformation Macaca fascicularis Neutralization Tests Promoter Regions (Genetics) Recombinant Proteins/IMMUNOLOGY Simian Acquired Immunodeficiency Syndrome/*IMMUNOLOGY SIV/GENETICS/*IMMUNOLOGY Vaccinia Virus/GENETICS ABSTRACT 910730
M9170960
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