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Hu SL; Moran PA; McClure J; Kosowski SG; Zarling JM; Morton W; Oncogen
November 30, 1988
Vaccines 87. Modern Approaches to New Vaccines: Prevention of AIDS and

Vaccinia virus has been used successfully as a vector for the expression of a variety of foreign genes. The potential use of recombinant vaccinia virus as a live vaccine against several infectious diseases has also been indicated. This technology could be applied for possible development of an acquired immune deficiency syndrome (AIDS) vaccine. A recombinant vaccinia virus had been constructed expressing the envelope glycoproteins of lymphadenopathy associated virus (LAV), an isolate of human immunodeficiency virus (HIV). Mice immunized with this recombinant (v-env5) produced antibodies that specifically recognized LAV envelope glycoproteins. These studies have been extended to a species of nonhuman primate, Macaca fascicularis, and it has been shown that the recombinant virus was able to elicit both humoral and cell-mediated immune responses to LAV. Eight macaques were inoculated with recombinant vaccinia virus v-env5; seven of these animals were inoculated again 12 wk after the primary inoculation, and their humoral response was studied. Only two animals seroconverted after the primary inoculation, but all seven animals became seropositive after the second inoculation. Sera from all these animals reacted strongly with gp41. To test whether the recombinant virus would also induce a T-cell-mediated immune response to HIV, peripheral blood lymphocytes (PBLs) from the immunized macaques were tested for their ability to proliferate and incorporate [3H]thymidine in response to stimulation by purified LAV virions. PBLs from all macaques immunized with v-env5, including the one that received only one inoculation, proliferated in vitro in response to stimulation by LAV. Immunization of macaques with recombinant vaccinia virus expressing LAV envelope glycoproteins causes both the generation of antibodies and T-cell-mediated immune responses to HIV. Since envelope antigens are the only LAV antigens encoded by the recombinant virus, it is apparent that the T cells which proliferate and produce interleukin-2 following LAV stimulation recognize LAV envelope antigens. Studies are in progress to determine whether immunization of chimpanzees with the same recombinant virus will induce both helper- and cytotoxic-T-cell responses to LAV and confer protection against infection with HIV. (5 Refs)

Acquired Immunodeficiency Syndrome/*IMMUNOLOGY Animal Antibodies, Viral/*ANALYSIS HIV/*IMMUNOLOGY Macaca fascicularis T-Lymphocytes/IMMUNOLOGY Vaccination Vaccines, Synthetic/ADMINISTRATION & DOSAGE/*IMMUNOLOGY Vaccinia Virus/*IMMUNOLOGY Viral Envelope Proteins/IMMUNOLOGY Viral Vaccines/ADMINISTRATION & DOSAGE/*IMMUNOLOGY MEETING PAPER