4.8 Article

Potent anti-viral activity of a trispecific HIV neutralizing antibody in SHIV-infected monkeys

Journal

CELL REPORTS
Volume 38, Issue 1, Pages -

Publisher

CELL PRESS
DOI: 10.1016/j.celrep.2021.110199

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Funding

  1. Intramural Research Program of the Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH
  2. National Cancer Institute, National Institutes of Health [75N91019D00024]

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The use of trispecific bNAbs can effectively reduce viremia and maintain low levels of virus in the body through immune control. Compared to single bNAbs, trispecific bNAbs can suppress the emergence of resistance and minimize the potential for immune escape.
Broadly neutralizing antibodies (bNAbs) represent an alternative to drug therapy for the treatment of HIV-1 infection. Immunotherapy with single bNAbs often leads to emergence of escape variants, suggesting a potential benefit of combination bNAb therapy. Here, a trispecific bNAb reduces viremia 100-to 1000-fold in viremic SHIV-infected macaques. After treatment discontinuation, viremia rebounds transiently and returns to low levels, through CD8-mediated immune control. These viruses remain sensitive to the trispecific antibody, despite loss of sensitivity to one of the parental bNAbs. Similarly, the trispecific bNAb suppresses the emergence of resistance in viruses derived from HIV-1-infected subjects, in contrast to parental bNAbs. Trispecific HIV-1 neutralizing antibodies, therefore, mediate potent antiviral activity in vivo and may minimize the potential for immune escape.

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