Abstract:
OBJECTIVE: To evaluate the hypothesis that appropriately formulated immunogens, while inducing an anamnestic response in SIV infected monkeys, could affect viral burden or delay the development of the disease. RESULTS: Six Macaca fascicularis (Mf) (23, 26, 8202, 4, C1, 8302) immunized with inactivated whole SIV virus and two unvaccinated naive Mf (203, 208) became persistently infected after challenge (i.v.) with live SIVmac251. One year after challenge, when no clinical symptoms of the disease were apparent except for a decline of CD4+ cells (range 100-300 cells/mm3), four Mf (23, 26, 8202, 203, group A) were inoculated (i.m.) with formaline inactivated whole SIVmac251, and the remaining four Mf (4, C1, 8302, 208, group B) with an immunogen derived from supernatant of a human T cell line. The schedule of treatment was designed so that all monkeys will receive during 4 months a total of 5 doses of either immunogen (200 micrograms/dose, i.m.), the first two being in Alum adjuvant. The following parameters were considered: plasma viremia, number of infected circulating cells (quantitative PCR DNA), anti-SIV antibody titers, modification of numbers of T (CD2, CD4, CD8) or B (CD20) cells, evolution of hematological patterns. To date, only data from one month after the start of the treatment (after two doses of immunogen) are available. The anti-SIV antibody titers remained unchanged in all monkeys. Numbers of CD20+ cells did not vary, whereas the numbers of CD2, CD4 and CD8 positive cells almost doubled in 4 (23, 26 group A; 4, C1 group B) out of 8 monkeys independently of the type of immunogen used. The same parameters did not vary in two other previously vaccinated monkeys (8202, in group A and 8302, in group B), while in unvaccinated but infected monkeys (203, in group A and 208, in group B) they appeared to decline, as expected in infected monkeys. These preliminary data suggest a non specific stimulatory effect on T but not on B cell populations following immunization of infected monkeys. Work is in progress to elucidate if these changes are stable and if the viral burden will also be affected.
Keywords: Animal Antigens, CD/ANALYSIS Antigens, CD4/ANALYSIS Antigens, CD8/ANALYSIS Antigens, Differentiation, B-Lymphocyte/ANALYSIS Antigens, Differentiation, T-Lymphocyte/ANALYSIS Antigens, Surface/ANALYSIS Cell Line DNA, Viral/ANALYSIS Human Immunization Schedule *Immunotherapy, Active Macaca fascicularis Polymerase Chain Reaction Receptors, Immunologic/ANALYSIS Simian Acquired Immunodeficiency Syndrome/IMMUNOLOGY/*THERAPY SIV/*IMMUNOLOGY/ISOLATION & PURIF T-Lymphocyte Subsets/IMMUNOLOGY T-Lymphocytes Vaccines, Inactivated/*THERAPEUTIC USE Viral Vaccines/*THERAPEUTIC USE ABSTRACT
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M9470920
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