This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.This project includes three main experiments to explore antibody approaches against the AIDS virus.EXPERIMENT 1:In this experiment we compared the antiviral efficacy of two broadly neutralizing monoclonal anti-HIV antibodies: clone 2F5 and 4E10. 16 animals were included in this experiment (6 animals per monoclonal antibody and 2 animals for the control group treated with indifferent antibody, and 2 animals for viral stock control without any antibody treatment). The 12 study animals received 50 mg/kg 2F5 or 50 mg/kg 4E10 antibody intravenously 24 hours prior to the viral challenge. The control animals received indifferent IgG1 antibody. To maintain the desired antibody level we repeated the antibody administration 1 day after the viral challenge. Viral challenge was performed on all treated and control animals by administering 2000 TCID50 SHIVBAL intrarectally.We have completed this experiment and found that with the exception of the control animals all of the macaques (12 animals) were protected against the viral challenge. We decided to test the longevity of the protection by challenging the animals again without further antibody administration. We performed the challenge on Jan 30-31 2008. We used the same route and viral stock for challenge (2000 TCID50 SHIVBAL intrarectally). Concurrently we challenged 2 na ve animals to assess the quality of the virus stock. At present we are monitoring the animals for viremia by measuring plasma viral load.EXPERIMENT 2:In this experiment we studied whether the monoclonal antibody 2G12 is more effective in vivo than predicted by its in vitro neutralization activity. 9 female animals were included in this experiment (5 animals for the 2G12 antibody treated group, 2 animals for the control group treated with indifferent antibody, and 2 animals for viral stock control without any antibody treatment). Prior to the antibody administration each animal received 30 mg Depo Provera i.m. in order to thin the vaginal epithelium and make the animals more susceptible to the viral challenge. To decrease possible preexisting genital tract inflammation that may affect the viral transmission we put the animals on a 7 day course of Baytril (Enrofloxacin) at a dose of 2.5 mg/kg BID (twice a day). This antibiotic regimen is in accordance to clinically prescribed regimens by the veterinarians of the Primate Center. 24 hours before viral challenge the animals were treated with 40 mg/kg 2G12 antibody intravenously. Viral challenge were performed on all treated and control animals by administering 500 TCID50 SHIV162P3 intravaginally. We will complete this experiment in early 2008. The results acquired so far show that of the 5 2G12 antibody treated animals 2 were completely protected, 1 animal showed signs of transient viremia and 2 animals became permanently viremic.EXPERIMENT 3:In this experiment we intend to determine whether continuous administration of a neutralizing antibody will provide a better protection than a single bolus of the same antibody against a mucosal SHIV challenge. Detailed experimental plans are under development. We have 13 animals set aside for this last project.These experiments used WNPRC Animal Services, Genetics Services, and Immunology & Virology Services.
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