Enhanced HIV-1 immunotherapy by commonly arising antibodies that target virus escape variants

Florian Klein; Lilian Nogueira; Yoshiaki Nishimura; Ganesh Phad; Anthony P. West; Ariel Halper-Stromberg; Joshua A. Horwitz; Anna Gazumyan; Cassie Liu; Thomas R. Eisenreich; Clara Lehmann; Gerd Fätkenheuer; Constance Williams; Masashi Shingai; Malcolm A. Martin; Pamela J. Bjorkman; Michael S. Seaman; Susan Zolla-Pazner; Gunilla B. Karlsson Hedestam; Michel C. Nussenzweig

doi:10.1084/jem.20141050

Enhanced HIV-1 immunotherapy by commonly arising antibodies that target virus escape variants

Florian Klein, Lilian Nogueira, Yoshiaki Nishimura, Ganesh Phad, Anthony P. West, Ariel Halper-Stromberg, Joshua A. Horwitz, Anna Gazumyan, Cassie Liu, Thomas R. Eisenreich, Clara Lehmann, Gerd Fätkenheuer, Constance Williams, Masashi Shingai, Malcolm A. Martin, Pamela J. Bjorkman, Michael S. Seaman, Susan Zolla-Pazner, Gunilla B. Karlsson Hedestam, Michel C. Nussenzweig

Research output: Contribution to journal › Article › peer-review

70 Scopus citations

Abstract

Antibody-mediated immunotherapy is effective in humanized mice when combinations of broadly neutralizing antibodies (bNAbs) are used that target nonoverlapping sites on the human immunodeficiency virus type 1 (HIV-1) envelope. In contrast, single bNAbs can control simian-human immunodeficiency virus (SHIV) infection in immune-competent macaques, suggesting that the host immune response might also contribute to the control of viremia. Here, we investigate how the autologous antibody response in intact hosts can contribute to the success of immunotherapy. We find that frequently arising antibodies that normally fail to control HIV-1 infection can synergize with passively administered bNAbs by preventing the emergence of bNAb viral escape variants.

Original language	English
Pages (from-to)	2361-2372
Number of pages	12
Journal	Journal of Experimental Medicine
Volume	211
Issue number	12
DOIs	https://doi.org/10.1084/jem.20141050
State	Published - 2014
Externally published	Yes

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Klein, F., Nogueira, L., Nishimura, Y., Phad, G., West, A. P., Halper-Stromberg, A., Horwitz, J. A., Gazumyan, A., Liu, C., Eisenreich, T. R., Lehmann, C., Fätkenheuer, G., Williams, C., Shingai, M., Martin, M. A., Bjorkman, P. J., Seaman, M. S., Zolla-Pazner, S., Karlsson Hedestam, G. B., & Nussenzweig, M. C. (2014). Enhanced HIV-1 immunotherapy by commonly arising antibodies that target virus escape variants. Journal of Experimental Medicine, 211(12), 2361-2372. https://doi.org/10.1084/jem.20141050

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title = "Enhanced HIV-1 immunotherapy by commonly arising antibodies that target virus escape variants",

abstract = "Antibody-mediated immunotherapy is effective in humanized mice when combinations of broadly neutralizing antibodies (bNAbs) are used that target nonoverlapping sites on the human immunodeficiency virus type 1 (HIV-1) envelope. In contrast, single bNAbs can control simian-human immunodeficiency virus (SHIV) infection in immune-competent macaques, suggesting that the host immune response might also contribute to the control of viremia. Here, we investigate how the autologous antibody response in intact hosts can contribute to the success of immunotherapy. We find that frequently arising antibodies that normally fail to control HIV-1 infection can synergize with passively administered bNAbs by preventing the emergence of bNAb viral escape variants.",

author = "Florian Klein and Lilian Nogueira and Yoshiaki Nishimura and Ganesh Phad and West, {Anthony P.} and Ariel Halper-Stromberg and Horwitz, {Joshua A.} and Anna Gazumyan and Cassie Liu and Eisenreich, {Thomas R.} and Clara Lehmann and Gerd F{\"a}tkenheuer and Constance Williams and Masashi Shingai and Martin, {Malcolm A.} and Bjorkman, {Pamela J.} and Seaman, {Michael S.} and Susan Zolla-Pazner and {Karlsson Hedestam}, {Gunilla B.} and Nussenzweig, {Michel C.}",

note = "Publisher Copyright: {\textcopyright} 2014 Klein et al.",

year = "2014",

doi = "10.1084/jem.20141050",

language = "English",

volume = "211",

pages = "2361--2372",

journal = "Journal of Experimental Medicine",

issn = "0022-1007",

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Klein, F, Nogueira, L, Nishimura, Y, Phad, G, West, AP, Halper-Stromberg, A, Horwitz, JA, Gazumyan, A, Liu, C, Eisenreich, TR, Lehmann, C, Fätkenheuer, G, Williams, C, Shingai, M, Martin, MA, Bjorkman, PJ, Seaman, MS, Zolla-Pazner, S, Karlsson Hedestam, GB & Nussenzweig, MC 2014, 'Enhanced HIV-1 immunotherapy by commonly arising antibodies that target virus escape variants', Journal of Experimental Medicine, vol. 211, no. 12, pp. 2361-2372. https://doi.org/10.1084/jem.20141050

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AU - Klein, Florian

AU - Nogueira, Lilian

AU - Nishimura, Yoshiaki

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AU - West, Anthony P.

AU - Halper-Stromberg, Ariel

AU - Horwitz, Joshua A.

AU - Gazumyan, Anna

AU - Liu, Cassie

AU - Eisenreich, Thomas R.

AU - Lehmann, Clara

AU - Fätkenheuer, Gerd

AU - Williams, Constance

AU - Shingai, Masashi

AU - Martin, Malcolm A.

AU - Bjorkman, Pamela J.

AU - Seaman, Michael S.

AU - Zolla-Pazner, Susan

AU - Karlsson Hedestam, Gunilla B.

AU - Nussenzweig, Michel C.

PY - 2014

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AB - Antibody-mediated immunotherapy is effective in humanized mice when combinations of broadly neutralizing antibodies (bNAbs) are used that target nonoverlapping sites on the human immunodeficiency virus type 1 (HIV-1) envelope. In contrast, single bNAbs can control simian-human immunodeficiency virus (SHIV) infection in immune-competent macaques, suggesting that the host immune response might also contribute to the control of viremia. Here, we investigate how the autologous antibody response in intact hosts can contribute to the success of immunotherapy. We find that frequently arising antibodies that normally fail to control HIV-1 infection can synergize with passively administered bNAbs by preventing the emergence of bNAb viral escape variants.

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Enhanced HIV-1 immunotherapy by commonly arising antibodies that target virus escape variants

Abstract

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