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 journalArticlepeer-review

69 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 languageEnglish
Pages (from-to)2361-2372
Number of pages12
JournalJournal of Experimental Medicine
Volume211
Issue number12
DOIs
StatePublished - 2014
Externally publishedYes

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