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

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. [Display omitted] • Trispecific bNAbs reduce viremia 100- to 1000-fold in viremic SHIV-infected macaques • After treatment completion in these macaques, long-term viral control is CD8-mediated • Trispecific but not parental bNAbs suppress the emergence of resistant virus in culture Immunotherapy with monoclonal bNAbs leads to emergence of escape variants. Pegu et al. show that trispecific bNAb treatment reduces viremia up to 1000-fold in vivo and limits selection of resistant HIV-1 variants in cell culture. Thus, this antibody has therapeutic potential and may minimize immune escape. [ABSTRACT FROM AUTHOR]