4.8 Article

Combination anti-HIV-1 antibody therapy is associated with increased virus-specific T cell immunity

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NATURE MEDICINE
卷 26, 期 2, 页码 222-+

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NATURE PORTFOLIO
DOI: 10.1038/s41591-019-0747-1

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资金

  1. Canadian Institutes for Health Research [152977, 154049]
  2. Canada Foundation for Innovation Program Leader grant [31756]
  3. FRQS AIDS and Infectious Diseases Network
  4. National Institutes of Health [UM1 AI-100663, AI-144462, R01AI-129795]
  5. Einstein-Rockefeller-CUNY Center for AIDS Research [1P30AI124414-01A1]
  6. BEAT-HIV Delaney grant [UM1 AI-126620]
  7. Robertson Fund
  8. Bill and Melinda Gates Foundation Collaboration for AIDS Vaccine Discovery [OPP1092074, OPP1124068]
  9. Quebec Health Research Fund (FRQS)
  10. Department of Microbiology, Immunology and Infectious Diseases, Universite de Montreal
  11. CIHR Fellowship Award [152536]
  12. Merit Award of the Quebec Health Research Fund (FRQS)

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T cell responses specific for HIV-1 Gag peptides increased in HIV-positive recipients of two broadly neutralizing antibodies with prolonged suppression of blood viremia during antiretroviral treatment interruption. Combination antiretroviral therapy (ART) is highly effective in controlling human immunodeficiency virus (HIV)-1 but requires lifelong medication due to the existence of a latent viral reservoir(1,2). Potent broadly neutralizing antibodies (bNAbs) represent a potential alternative or adjuvant to ART. In addition to suppressing viremia, bNAbs may have T cell immunomodulatory effects as seen for other forms of immunotherapy(3). However, this has not been established in individuals who are infected with HIV-1. Here, we document increased HIV-1 Gag-specific CD8(+) T cell responses in the peripheral blood of all nine study participants who were infected with HIV-1 with suppressed blood viremia, while receiving bNAb therapy during ART interruption(4). Increased CD4(+) T cell responses were detected in eight individuals. The increased T cell responses were due both to newly detectable reactivity to HIV-1 Gag epitopes and the expansion of pre-existing measurable responses. These data demonstrate that bNAb therapy during ART interruption is associated with enhanced HIV-1-specific T cell responses. Whether these augmented T cell responses can contribute to bNAb-mediated viral control remains to be determined.

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