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. Neutralizing antibodies are important for HIV vaccines. Passive antibody transfer has shown that neutralizing antibodies, at high concentrations, protect from vaginal challenge with pathogenic SHIVs bearing the HIV-1 envelope. The mechanisms of protection by neutralizing antibody and, in particular, the role of Fc-mediated effector function have not been defined. The role of secretory IgA and the interplay between mucosal and systemic neutralizing antibodies is probably important but has not been studied.The challenge protocol is being revised to test deterimine the lowest infectious dose. In January, 2007, 3 animals were treated with Depo-provera and continue on treatment every 21 days to maintain a thinned vaginal epithelium. Every Thursday from 1/25/07 to 3/1/07 animals were treated with control [ PBS] at a dose equivalent to 1 ml/kg of b12 antibody intravenously. Two of three animals were challenged with a dose of 3 TCID50 twice weekly following control treatment for 8 challenges and then 10 TCID50 for 3 challenges. The remaining animal was challenged with 3 TCID50 twice weekly following control treatment for four challenges and then 10 TCID50 for 7 challenges, the last challenge on 3/5/07. One animal in group 1 became positive by PCR in blood taken on 3/1/07, one from the second group became positive by PCR on blood from 3/5/07. Treatment will continue weekly with 10 TCID50 for the final animal in group 1 for three weeks or until positive by PCR. Plasma samples were being collected before each challenge for vPCR for virus. Results will be used to finalize the dose for the experimental groups. Twelve animals receive antibody administration [either PBS (n=2; 1 ml/kg), LL mutant b12 (n=5; 1 mg/kg), or b12 wild type antibody (n=5; 1 mg/kg)] challenges and follow-up as described above and refined by the experiment above.
Showing the most recent 10 out of 352 publications
