Antibody 10-1074 suppresses viremia in HIV-1-infected individuals

Marina Caskey; Till Schoofs; Henning Gruell; Allison Settler; Theodora Karagounis; Edward F. Kreider; Ben Murrell; Nico Pfeifer; Lilian Nogueira; Thiago Y. Oliveira; Gerald H. Learn; Yehuda Z. Cohen; Clara Lehmann; Daniel Gillor; Irina Shimeliovich; Cecilia Unson-O'Brien; Daniela Weiland; Alexander Robles; Tim Kümmerle; Christoph Wyen; Rebeka Levin; Maggi Witmer-Pack; Kemal Eren; Caroline Ignacio; Szilard Kiss; Anthony P. West; Hugo Mouquet; Barry S. Zingman; Roy M. Gulick; Tibor Keler; Pamela J. Bjorkman; Michael S. Seaman; Beatrice H. Hahn; Gerd Fätkenheuer; Sarah J. Schlesinger; Michel C. Nussenzweig; Florian Klein

doi:10.1038/nm.4268

Antibody 10-1074 suppresses viremia in HIV-1-infected individuals

Marina Caskey, Till Schoofs, Henning Gruell, Allison Settler, Theodora Karagounis, Edward F. Kreider, Ben Murrell, Nico Pfeifer, Lilian Nogueira, Thiago Y. Oliveira, Gerald H. Learn, Yehuda Z. Cohen, Clara Lehmann, Daniel Gillor, Irina Shimeliovich, Cecilia Unson-O'Brien, Daniela Weiland, Alexander Robles, Tim Kümmerle, Christoph WyenRebeka Levin, Maggi Witmer-Pack, Kemal Eren, Caroline Ignacio, Szilard Kiss, Anthony P. West, Hugo Mouquet, Barry S. Zingman, Roy M. Gulick, Tibor Keler, Pamela J. Bjorkman, Michael S. Seaman, Beatrice H. Hahn, Gerd Fätkenheuer, Sarah J. Schlesinger, Michel C. Nussenzweig, Florian Klein

Medicine

Research output: Contribution to journal › Article

163 Scopus citations

Abstract

Monoclonal antibody 10-1074 targets the V3 glycan supersite on the HIV-1 envelope (Env) protein. It is among the most potent anti-HIV-1 neutralizing antibodies isolated so far. Here we report on its safety and activity in 33 individuals who received a single intravenous infusion of the antibody. 10-1074 was well tolerated and had a half-life of 24.0 d in participants without HIV-1 infection and 12.8 d in individuals with HIV-1 infection. Thirteen individuals with viremia received the highest dose of 30 mg/kg 10-1074. Eleven of these participants were 10-1074-sensitive and showed a rapid decline in viremia by a mean of 1.52 log 10 copies/ml. Virologic analysis revealed the emergence of multiple independent 10-1074-resistant viruses in the first weeks after infusion. Emerging escape variants were generally resistant to the related V3-specific antibody PGT121, but remained sensitive to antibodies targeting nonoverlapping epitopes, such as the anti-CD4-binding-site antibodies 3BNC117 and VRC01. The results demonstrate the safety and activity of 10-1074 in humans and support the idea that antibodies targeting the V3 glycan supersite might be useful for the treatment and prevention of HIV-1 infection.

Original language	English (US)
Pages (from-to)	185-191
Number of pages	7
Journal	Nature Medicine
Volume	23
Issue number	2
DOIs	https://doi.org/10.1038/nm.4268
State	Published - Feb 1 2017

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)

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10.1038/nm.4268

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Caskey, M., Schoofs, T., Gruell, H., Settler, A., Karagounis, T., Kreider, E. F., Murrell, B., Pfeifer, N., Nogueira, L., Oliveira, T. Y., Learn, G. H., Cohen, Y. Z., Lehmann, C., Gillor, D., Shimeliovich, I., Unson-O'Brien, C., Weiland, D., Robles, A., Kümmerle, T., ... Klein, F. (2017). Antibody 10-1074 suppresses viremia in HIV-1-infected individuals. Nature Medicine, 23(2), 185-191. https://doi.org/10.1038/nm.4268

Antibody 10-1074 suppresses viremia in HIV-1-infected individuals. / Caskey, Marina; Schoofs, Till; Gruell, Henning; Settler, Allison; Karagounis, Theodora; Kreider, Edward F.; Murrell, Ben; Pfeifer, Nico; Nogueira, Lilian; Oliveira, Thiago Y.; Learn, Gerald H.; Cohen, Yehuda Z.; Lehmann, Clara; Gillor, Daniel; Shimeliovich, Irina; Unson-O'Brien, Cecilia; Weiland, Daniela; Robles, Alexander; Kümmerle, Tim; Wyen, Christoph; Levin, Rebeka; Witmer-Pack, Maggi; Eren, Kemal; Ignacio, Caroline; Kiss, Szilard; West, Anthony P.; Mouquet, Hugo; Zingman, Barry S.; Gulick, Roy M.; Keler, Tibor; Bjorkman, Pamela J.; Seaman, Michael S.; Hahn, Beatrice H.; Fätkenheuer, Gerd; Schlesinger, Sarah J.; Nussenzweig, Michel C.; Klein, Florian.

In: Nature Medicine, Vol. 23, No. 2, 01.02.2017, p. 185-191.

Research output: Contribution to journal › Article

Caskey, M, Schoofs, T, Gruell, H, Settler, A, Karagounis, T, Kreider, EF, Murrell, B, Pfeifer, N, Nogueira, L, Oliveira, TY, Learn, GH, Cohen, YZ, Lehmann, C, Gillor, D, Shimeliovich, I, Unson-O'Brien, C, Weiland, D, Robles, A, Kümmerle, T, Wyen, C, Levin, R, Witmer-Pack, M, Eren, K, Ignacio, C, Kiss, S, West, AP, Mouquet, H, Zingman, BS, Gulick, RM, Keler, T, Bjorkman, PJ, Seaman, MS, Hahn, BH, Fätkenheuer, G, Schlesinger, SJ, Nussenzweig, MC & Klein, F 2017, 'Antibody 10-1074 suppresses viremia in HIV-1-infected individuals', Nature Medicine, vol. 23, no. 2, pp. 185-191. https://doi.org/10.1038/nm.4268

Caskey, Marina ; Schoofs, Till ; Gruell, Henning ; Settler, Allison ; Karagounis, Theodora ; Kreider, Edward F. ; Murrell, Ben ; Pfeifer, Nico ; Nogueira, Lilian ; Oliveira, Thiago Y. ; Learn, Gerald H. ; Cohen, Yehuda Z. ; Lehmann, Clara ; Gillor, Daniel ; Shimeliovich, Irina ; Unson-O'Brien, Cecilia ; Weiland, Daniela ; Robles, Alexander ; Kümmerle, Tim ; Wyen, Christoph ; Levin, Rebeka ; Witmer-Pack, Maggi ; Eren, Kemal ; Ignacio, Caroline ; Kiss, Szilard ; West, Anthony P. ; Mouquet, Hugo ; Zingman, Barry S. ; Gulick, Roy M. ; Keler, Tibor ; Bjorkman, Pamela J. ; Seaman, Michael S. ; Hahn, Beatrice H. ; Fätkenheuer, Gerd ; Schlesinger, Sarah J. ; Nussenzweig, Michel C. ; Klein, Florian. / Antibody 10-1074 suppresses viremia in HIV-1-infected individuals. In: Nature Medicine. 2017 ; Vol. 23, No. 2. pp. 185-191.

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abstract = "Monoclonal antibody 10-1074 targets the V3 glycan supersite on the HIV-1 envelope (Env) protein. It is among the most potent anti-HIV-1 neutralizing antibodies isolated so far. Here we report on its safety and activity in 33 individuals who received a single intravenous infusion of the antibody. 10-1074 was well tolerated and had a half-life of 24.0 d in participants without HIV-1 infection and 12.8 d in individuals with HIV-1 infection. Thirteen individuals with viremia received the highest dose of 30 mg/kg 10-1074. Eleven of these participants were 10-1074-sensitive and showed a rapid decline in viremia by a mean of 1.52 log 10 copies/ml. Virologic analysis revealed the emergence of multiple independent 10-1074-resistant viruses in the first weeks after infusion. Emerging escape variants were generally resistant to the related V3-specific antibody PGT121, but remained sensitive to antibodies targeting nonoverlapping epitopes, such as the anti-CD4-binding-site antibodies 3BNC117 and VRC01. The results demonstrate the safety and activity of 10-1074 in humans and support the idea that antibodies targeting the V3 glycan supersite might be useful for the treatment and prevention of HIV-1 infection.",

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