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


ABSTRACT: 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.

SUBMITTER: Pegu A 

PROVIDER: S-EPMC8767641 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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

Pegu Amarendra A   Xu Ling L   DeMouth Megan E ME   Fabozzi Giulia G   March Kylie K   Almasri Cassandra G CG   Cully Michelle D MD   Wang Keyun K   Yang Eun Sung ES   Dias Joana J   Fennessey Christine M CM   Hataye Jason J   Wei Ronnie R RR   Rao Ercole E   Casazza Joseph P JP   Promsote Wanwisa W   Asokan Mangaiarkarasi M   McKee Krisha K   Schmidt Stephen D SD   Chen Xuejun X   Liu Cuiping C   Shi Wei W   Geng Hui H   Foulds Kathryn E KE   Kao Shing-Fen SF   Noe Amy A   Li Hui H   Shaw George M GM   Zhou Tongqing T   Petrovas Constantinos C   Todd John-Paul JP   Keele Brandon F BF   Lifson Jeffrey D JD   Doria-Rose Nicole A NA   Koup Richard A RA   Yang Zhi-Yong ZY   Nabel Gary J GJ   Mascola John R JR  

Cell reports 20220101 1


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 sen  ...[more]

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