Badamchi-Zadeh, AlexanderTartaglia, LawrenceAbbink, PeterBricault, ChristineLiu, Po-TingBoyd, MichaelKirilova, MarinelaMercado, Noe B.Nanayakkara, Ovini S.Vrbanac, Vladimir D.Tager, Andrew M.Larocca, RafaelSeaman, MichaelBarouch, Dan2018-06-272018Badamchi-Zadeh, A., L. J. Tartaglia, P. Abbink, C. A. Bricault, P. Liu, M. Boyd, M. Kirilova, et al. 2018. “Therapeutic Efficacy of Vectored PGT121 Gene Delivery in HIV-1-Infected Humanized Mice.” Journal of Virology 92 (7): e01925-17. doi:10.1128/JVI.01925-17. http://dx.doi.org/10.1128/JVI.01925-17.http://nrs.harvard.edu/urn-3:HUL.InstRepos:37160360ABSTRACT Broadly neutralizing antibodies (bNAbs) are being explored for HIV-1 prevention and cure strategies. However, administration of purified bNAbs poses challenges in resource-poor settings, where the HIV-1 disease burden is greatest. In vivo vector-based production of bNAbs represents an alternative strategy. We investigated adenovirus serotype 5 (Ad5) and adeno-associated virus serotype 1 (AAV1) vectors to deliver the HIV-1-specific bNAb PGT121 in wild-type and immunocompromised C57BL/6 mice as well as in HIV-1-infected bone marrow-liver-thymus (BLT) humanized mice. Ad5.PGT121 and AAV1.PGT121 produced functional antibody in vivo. Ad5.PGT121 produced PGT121 rapidly within 6 h, whereas AAV1.PGT121 produced detectable PGT121 in serum by 72 h. Serum PGT121 levels were rapidly reduced by the generation of anti-PGT121 antibodies in immunocompetent mice but were durably maintained in immunocompromised mice. In HIV-1-infected BLT humanized mice, Ad5.PGT121 resulted in a greater reduction of viral loads than did AAV1.PGT121. Ad5.PGT121 also led to more-sustained virologic control than purified PGT121 IgG. Ad5.PGT121 afforded more rapid, robust, and durable antiviral efficacy than AAV1.PGT121 and purified PGT121 IgG in HIV-1-infected humanized mice. Further evaluation of vector delivery of HIV-1 bNAbs is warranted, although approaches to prevent the generation of antiantibody responses may also be required. IMPORTANCE: Broadly neutralizing antibodies (bNAbs) are being explored for HIV-1 prevention and cure strategies, but delivery of purified antibodies may prove challenging. We investigated adenovirus serotype 5 (Ad5) and adeno-associated virus serotype 1 (AAV1) vectors to deliver the HIV-1-specific bNAb PGT121. Ad5.PGT121 afforded more rapid, robust, and durable antiviral efficacy than AAV1.PGT121 and purified PGT121 IgG in HIV-1-infected humanized mice.en-USHIV-1PGT121adeno-associated virusadenovirusesneutralizing antibodiesJournal Article2018-06-2710.1128/JVI.01925-17