@article{a35cbfef0a1a46e2aef29b4fcd984ead,
title = "Long-Term Delivery of an Anti-SIV Monoclonal Antibody With AAV",
abstract = "Long-term delivery of anti-HIV monoclonal antibodies using adeno-associated virus (AAV) holds promise for the prevention and treatment of HIV infection. We previously reported that after receiving a single administration of AAV vector coding for anti-SIV antibody 5L7, monkey 84-05 achieved high levels of AAV-delivered 5L7 IgG1 in vivo which conferred sterile protection against six successive, escalating dose, intravenous challenges with highly infectious, highly pathogenic SIVmac239, including a final challenge with 10 animal infectious doses (1). Here we report that monkey 84-05 has successfully maintained 240–350 μg/ml of anti-SIV antibody 5L7 for over 6 years. Approximately 2% of the circulating IgG in this monkey is this one monoclonal antibody. This monkey generated little or no anti-drug antibodies (ADA) to the AAV-delivered antibody for the duration of the study. Due to the nature of the high-dose challenge used and in order to rule out a potential low-level infection not detected by regular viral loads, we have used ultrasensitive techniques to detect cell-associated viral DNA and RNA in PBMCs from this animal. In addition, we have tested serum from 84-05 by ELISA against overlapping peptides spanning the whole envelope sequence for SIVmac239 (PepScan) and against recombinant p27 and gp41 proteins. No reactivity has been detected in the ELISAs indicating the absence of naturally arising anti-SIV antibodies; moreover, the ultrasensitive cell-associated viral tests yielded no positive reaction. We conclude that macaque 84-05 was effectively protected and remained uninfected. Our data show that durable, continuous antibody expression can be achieved after one single administration of AAV and support the potential for lifelong protection against HIV from a single vector administration.",
keywords = "AAV vector, HIV/SIV cure, broadly neutralizing antibodies, gene therapy, immunotherapy, long-term expression, prophylaxis, rhesus monkeys",
author = "Martinez-Navio, {Jos{\'e} M.} and Fuchs, {Sebastian P.} and Mendes, {Desiree E.} and Rakasz, {Eva G.} and Guangping Gao and Lifson, {Jeffrey D.} and Desrosiers, {Ronald C.}",
note = "Funding Information: The authors thank Kimberly L. Weisgrau and Jessica Furlott for technical assistance; the Gene Therapy Core at the University of Massachusetts Medical School for excellent AAV vector preparation; the Wisconsin National Primate Research Center veterinary staff for professional animal care; Nancy Schultz-Darken, Wendy Newton, and Eric Alexander for animal experiment planning and conduct; and William J. Bosche, Randy Fast, Michael Hull, Kelli Oswald, and Rebecca Shoemaker of the Quantitative Molecular Virology Core in the AIDS and Cancer Virus Program of the Frederick National Laboratory for Cancer Research for expert technical assistance with viral quantitation. Funding. This project was supported by National Institutes of Health (NIH) grants P01 AI100263, R01 AI098446, and U19 AI095985 (to RD) and by P51 base grant RR000167 (Wisconsin National Primate Research Center) from the NIH. We also acknowledge support from the Miami Center for AIDS Research (to JM-N and to SF) at the University of Miami Miller School of Medicine funded by grant P30AI073961 from the NIH. This project has been funded in part with federal funds from the National Cancer Institute, NIH, under contracts HHSN261200800001E and 75N91019D00024 (JL). Funding Information: This project was supported by National Institutes of Health (NIH) grants P01 AI100263, R01 AI098446, and U19 AI095985 (to RD) and by P51 base grant RR000167 (Wisconsin National Primate Research Center) from the NIH. We also acknowledge support from the Miami Center for AIDS Research (to JM-N and to SF) at the University of Miami Miller School of Medicine funded by grant P30AI073961 from the NIH. This project has been funded in part with federal funds from the National Cancer Institute, NIH, under contracts HHSN261200800001E and 75N91019D00024 (JL).",
year = "2020",
month = mar,
day = "17",
doi = "10.3389/fimmu.2020.00449",
language = "English (US)",
volume = "11",
journal = "Frontiers in Immunology",
issn = "1664-3224",
publisher = "Frontiers Media S. A.",
}