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

2014; Rockefeller University Press; Volume: 211; Issue: 12 Linguagem: Inglês

10.1084/jem.20141050

1540-9538

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

T-cell and B-cell Immunology

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.