Important note: Information in this article was accurate in 1989. The state of the art may have changed since the publication date.
PREPARATION AND EVALUATION OF A HUMAN IMMUNODEFICIENCY VIRUS GP120 PROTOTYPE VACCINE
Vaccines 88. New Chemical and Genetic Approaches to Vaccination: Prevention of AIDS and Other Viral, Bacterial, and Parasitic Diseases. Ginsberg H et al, eds. New York, Cold Spring Harbor Laboratory, p. 277-82, 1988.. Unique Identifier : AIDSLINE ICDB/89649769 Arthur LO; Pyle SW; Bess JW Jr; Gilden RV; Nara PL; Robey WG; Fischinger PJ; Kelliher JC; Program Resources, Inc., NCI-Federick Cancer Res. Facility,; Frederick, MD 21701
Abstract:
The immune responses of chimpanzees immunized with a prototype HIV external glycoprotein vaccine were analyzed. Binding of gp120, the major envelope glycoprotein of HIV, to the CD4 molecules of T4-positive cells is considered an initial step in HIV infection and, as such, an immune response to gp120 may be effective in eliminating HIV-infected cells. The native glycoprotein was used because it should contain the post-translational modifications present on gp120 on the virus and virus-infected cells. Chimpanzees were inoculated with gp120 (50 ug) using alum as the adjuvant because it is the only adjuvant currently acceptable for human use. Immunizations were given subsequently on days 35, 63, and 150 following the first injection. Serum from immunized animals had a max 125I-labeled gp120 precipitating response 2 wk following each immunization. The humoral response to gp120 decayed rapidly after each immunization. The sera from all gp120-immunized animals neutralized human T-lymphotropic virus IIIB. Virus-neutralizing titers paralleled the precipitation titers, with max neutralizing antibody levels detected 2 wk after the fourth vaccination. The chimpanzee can be infected readily with HIV and, as such, will serve as a vaccine efficacy model. Infection can be followed by isolation of virus and seroconversion. Since HIV-infected chimpanzees have antibodies to the core antigen, p24, and gp120-vaccinated animals do not, seroconversion to p24 can be used as an index of infection in gp120-vaccinated chimpanzees. The type-specific neutralization response in the vaccinated chimpanzees will mandate an initial challenge with the homologous virus prior to any evaluation of protection against an HIV variant or HIV-infected cells. In addition, the rapid decrease in antibody levels following immunization with gp120 is a cause for concern. (7 Refs)
Keywords: Acquired Immunodeficiency Syndrome/*IMMUNOLOGY/PREVENTION & CONTROL Animal Chimpansee troglodytes HIV/*IMMUNOLOGY HIV Antibodies/BIOSYNTHESIS Neutralization Tests Retroviridae Proteins/*IMMUNOLOGY Vaccines, Synthetic/ADMINISTRATION & DOSAGE/*IMMUNOLOGY Viral Vaccines/ADMINISTRATION & DOSAGE/*IMMUNOLOGY MEETING PAPER
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