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

• Published in: Cell reports (Cambridge) Vol. 38; no. 1; p. 110199
• Main Authors: Pegu, Amarendra, Xu, Ling, DeMouth, Megan E., Fabozzi, Giulia, March, Kylie, Almasri, Cassandra G., Cully, Michelle D., Wang, Keyun, Yang, Eun Sung, Dias, Joana, Fennessey, Christine M., Hataye, Jason, Wei, Ronnie R., Rao, Ercole, Casazza, Joseph P., Promsote, Wanwisa, Asokan, Mangaiarkarasi, McKee, Krisha, Schmidt, Stephen D., Chen, Xuejun, Liu, Cuiping, Shi, Wei, Geng, Hui, Foulds, Kathryn E., Kao, Shing-Fen, Noe, Amy, Li, Hui, Shaw, George M., Zhou, Tongqing, Petrovas, Constantinos, Todd, John-Paul, Keele, Brandon F., Lifson, Jeffrey D., Doria-Rose, Nicole A., Koup, Richard A., Yang, Zhi-yong, Nabel, Gary J., Mascola, John R.
• Format: Journal Article
• Language: English
• Published: United States 04.01.2022
• Subjects: Animals; Antiviral Agents - therapeutic use; Broadly Neutralizing Antibodies - immunology; Broadly Neutralizing Antibodies - therapeutic use; CD8-Positive T-Lymphocytes - immunology; Cell Line, Tumor; HIV Antibodies - immunology; HIV Antibodies - therapeutic use; HIV-1 - immunology; Humans; Immune Evasion - immunology; Immunotherapy - methods; Macaca mulatta; Simian Acquired Immunodeficiency Syndrome - therapy; Simian Immunodeficiency Virus - immunology; THP-1 Cells; Viremia - prevention & control; Viremia - therapy
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2021.110199

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.