4.7 Article

Immunotherapy during the acute SHIV infection of macaques confers long-term suppression of viremia

Journal

JOURNAL OF EXPERIMENTAL MEDICINE
Volume 218, Issue 1, Pages -

Publisher

ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20201214

Keywords

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Funding

  1. Intramural Research Programof the National Institute of Allergy and Infectious Diseases, National Institutes of Health
  2. Bill and Melinda Gates Foundation Collaboration for AIDS Vaccine Discovery grants [OPP1092074, OPP1124068]
  3. National Institute of Allergy and Infectious Diseases of the National Institutes of Health [HIVRAD P01 AI100148]
  4. National Institutes of Health Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery grant [1UM1 AI100663-01]
  5. Robertson Foundation of Rockefeller University
  6. National Institutes of Health/National Institute of Allergy and Infectious Diseases grant [P01 AI138212]

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The study found that combination bNAb immunotherapy initiated on day 3 post-infection maintained durable CD8(+) T cell-mediated suppression of SHIVAD8 viremia and CD4(+) T cell levels in most of the treated monkeys during nearly 6 years of observation, with CD8(+) T cell immunity being the principal correlate of virus control. Treatment interventions beginning on week 2 post-infection also conferred controller status to some monkeys, but the time to suppression of plasma viremia was significantly delayed compared to early intervention on day 3.
We report that combination bNAb immunotherapy initiated on day 3 post-infection (PI) maintained durable CD8(+) T cell-mediated suppression of SHIVAD8 viremia and preinoculation levels of CD4(+) T cells in 9 of 13 treated monkeys during nearly 6 yr of observation, as assessed by successive CD8(+) T cell-depletion experiments. In an extension of that study, two treatment interventions (bNAbs alone or cART plus bNAbs) beginning on week 2 PI were conducted and conferred controller status to 7 of 12 monkeys that was also dependent on control mediated by CD8(+) cells. However, the median time to suppression of plasma viremia following intervention on week 2 was markedly delayed (85 wk) compared with combination bNAb immunotherapy initiated on day 3 (39 wk). In both cases, the principal correlate of virus control was the induction of CD8(+) T cellular immunity.

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