A vaccine against human immunodeficiency virus (HIV) would be highly effective in stopping the acquired immunodeficiency syndrome (AIDS) epidemic. A comprehensive evaluation of potential vaccine methodologies can be made by means of the simian model for AIDS, which takes advantage of the similarities in viral composition and disease potential between simian immunodeficiency virus (SIV) infection of rhesus macaques and HIV infection in humans. Immunization with a formalin-inactivated whole SIV vaccine potentiated with either alum and the Syntex adjuvant threonyl muramyl dipeptide (MDP) or MDP alone resulted in the protection of eight of nine rhesus monkeys challenged with ten animal-infectious doses of pathogenic virus. These results demonstrate that a whole virus vaccine is highly effective in inducing immune responses that can protect against lentivirus infection and AIDS-like disease.
The effects of initiating treatment with 3'-azido-3'-deoxythymidine (zidovudine) at different times after inoculation of simian immunodeficiency virus (SIV) were investigated in rhesus monkeys. Zidovudine treatments of 100 mg/kg/day (25 mg/kg, subcutaneously every 6 h) were initiated 1, 8, 24, or 72 h after intravenous inoculation of 10 ID50 of SIV. Treatments continued for 28 days, and results were compared with those of saline-treated controls. Serum infectious virus titers 14 days after inoculation (AI) significantly decreased after treatment initiation 1, 8, or 24 h AI. Titers were correlated with the time treatment was initiated. Treatments initiated 1-72 h AI prevented the establishment of persistent SIV antigenemia; greater effects were observed with earlier initiation of treatment. Treatments initiated 1-8 h AI resulted in decreased levels of viral antigenemia 14 days AI and delayed decreases in CD4+CD29+ blood lymphocytes. Earlier treatment initiation resulted in delayed recurrence of antigenemia, with a tendency for longer survival. Early initiation of treatment may be important for limiting initial viral replication and dissemination in cases of known exposure.
Seven 72-hr-old Indian origin rhesus monkeys (Macaca mulatta) were inoculated with 10 animal ID50 of SIV/DeltaB670. Nine age-matched animals were used as uninoculated controls. All seven inoculated animals became infected as verified by viral isolation and SIV p26 antigenemia. Five of seven infected animals died within a mean of 31 days (range, 26-41 days), with high levels of antigenemia beginning 1-2 weeks postinoculation (PI) that persisted until death. Absolute lymphocyte numbers were within normal limits in all animals in both groups throughout the study. Inoculated animals that died within a mean of 31 days (short-term survivors) had significantly lower numbers of CD4+CD29+ (helper/inducer) lymphocytes than did long-term surviving inoculated animals through 3 weeks PI. Numbers of CD4+ lymphocytes were no different when controls were compared to all inoculated animals through 4-5 weeks PI. The two inoculated animals surviving 216 and 423 days PI (long-term survivors) did demonstrate declining CD4+ cells, but only late in disease. CD8+ lymphocytes were significantly lower in short-term survivors when compared to long-term survivors through 5 weeks PI. Antibody production against SIV viral proteins was detected only in the long-term survivors and was similar to results from past studies in juveniles. Clinical signs in the inoculated group were consistent with those seen in past studies on older animals. Persistent bacterial infections, primarily of the GI and respiratory tracts, were seen in the infected group. Aside from the lack of some opportunistic infections such as cytomegalovirus (CMV) and Pneumocystis carinii, necropsy findings were not different when compared to past studies on juvenile animals.(ABSTRACT TRUNCATED AT 250 WORDS)
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