1. Safety and tolerability of AAV8 delivery of a broadly neutralizing antibody in adults living with HIV: a phase 1, dose-escalation trial
- Author
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Casazza, Joseph P., Cale, Evan M., Narpala, Sandeep, Yamshchikov, Galina V., Coates, Emily E., Hendel, Cynthia S., Novik, Laura, Holman, LaSonji A., Widge, Alicia T., Apte, Preeti, Gordon, Ingelise, Gaudinski, Martin R., Conan-Cibotti, Michelle, Lin, Bob C., Nason, Martha C., Trofymenko, Olga, Telscher, Shinyi, Plummer, Sarah H., Wycuff, Diane, Adams, William C., Pandey, Janardan P., McDermott, Adrian, Roederer, Mario, Sukienik, Avery N., O'Dell, Sijy, Gall, Jason G., Flach, Britta, Terry, Travis L., Choe, Misook, Shi, Wei, Chen, Xuejun, Kaltovich, Florence, Saunders, Kevin O., Stein, Judy A., Doria-Rose, Nicole A., Schwartz, Richard M., Balazs, Alejandro B., Baltimore, David, Nabel, Gary J., Koup, Richard A., Graham, Barney S., Ledgerwood, Julie E., Mascola, John R., Andrews, Charla, Arthur, Anita, Awan, Seemal F., Beck, Allison, Burch, Eugeania, Burgos Florez, Maria C., Berkowitz, Nina M., Boritz, Eli A., Carlton, Kevin, Cartagena, Cora T., Carter, Christina, Chen, Grace L., Costner, Pamela, Cunningham, Jennifer, Douek, Daniel C., Eshun, Aba M., Evans, Catina, Hicks, Renunda, Houser, Katherine V., Jones, Justine, Larkin, Brenda, Le, Lam, Mendoza, Floreliz, Migueles, Stephen, Misasi, John, Nguyen, Thuy A., Ola, Abidemi, Parker, Karen, Pittman, Iris, Requilman, La’ Shawn, Rothwell, Ro Shauna, Schieber, Gretchen L., Saunders, Jamie, Sitar, Sandra, Tran, Colin, Vasilenko, Olga, Waheed, Sana, Wang, Lingshu, Wang, Xiaolin, Whalen, William, Williams, Pernell, Wu, Richard L., and Zephir, Kathy
- Subjects
Adult ,HIV-1 ,Humans ,HIV Infections ,General Medicine ,Dependovirus ,HIV Antibodies ,Antibodies, Neutralizing ,General Biochemistry, Genetics and Molecular Biology ,Article ,Broadly Neutralizing Antibodies - Abstract
Adeno-associated viral vector-mediated transfer of DNA coding for broadly neutralizing anti-HIV antibodies (bnAbs) offers an alternative to attempting to induce protection by vaccination or by repeated infusions of bnAbs. In this study, we administered a recombinant bicistronic adeno-associated virus (AAV8) vector coding for both the light and heavy chains of the potent broadly neutralizing HIV-1 antibody VRC07 (AAV8-VRC07) to eight adults living with HIV. All participants remained on effective anti-retroviral therapy (viral load (VL) 1 μg ml(−1) in three individuals. In four individuals, VRC07 serum concentrations remained stable near maximal concentration for up to 3 years of follow-up. In exploratory analyses, neutralizing activity of in vivo produced VRC07 was similar to that of in vitro produced VRC07. Three of eight participants showed a non-idiotypic anti-drug antibody (ADA) response directed against the Fab portion of VRC07. This ADA response appeared to decrease the production of serum VRC07 in two of these three participants. These data represent a proof of concept that adeno-associated viral vectors can durably produce biologically active, difficult-to-induce bnAbs in vivo, which could add valuable new tools to the fight against infectious diseases.
- Published
- 2022