Anti-Drug Antibodies in Pigtailed Macaques Receiving HIV Broadly Neutralising Antibody PGT121

被引:4
|
作者
Lee, Wen Shi [1 ]
Reynaldi, Arnold [2 ]
Amarasena, Thakshila [1 ]
Davenport, Miles P. [2 ]
Parsons, Matthew S. [1 ,3 ,4 ]
Kent, Stephen J. [1 ,5 ]
机构
[1] Univ Melbourne, Peter Doherty Inst Infect & Immun, Dept Microbiol & Immunol, Melbourne, Vic, Australia
[2] Univ New South Wales, Kirby Inst, Kensington, NSW, Australia
[3] Emory Univ, Sch Med, Dept Pathol, Lab Med, Atlanta, GA 30322 USA
[4] Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30322 USA
[5] Monash Univ, Cent Clin Sch, Melbourne Sexual Hlth Ctr & Dept Infect Dis, Melbourne, Vic, Australia
来源
FRONTIERS IN IMMUNOLOGY | 2021年 / 12卷
基金
美国国家卫生研究院; 英国医学研究理事会;
关键词
HIV; broadly neutralizing antibodies (bNAb); PGT121; anti-drug antibodies (ADA); pigtailed macaque; MONOCLONAL-ANTIBODIES; NONHUMAN-PRIMATES; PROTECTION; VIREMIA; DELIVERY;
D O I
10.3389/fimmu.2021.749891
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Broadly neutralising antibodies (bNAbs) may play an important role in future strategies for HIV control. The development of anti-drug antibody (ADA) responses can reduce the efficacy of passively transferred bNAbs but the impact of ADA is imperfectly understood. We previously showed that therapeutic administration of the anti-HIV bNAb PGT121 (either WT or LALA version) controlled viraemia in pigtailed macaques with ongoing SHIV infection. We now report on 23 macaques that had multiple treatments with PGT121. We found that an increasing number of intravenous doses of PGT121 or human IgG1 isotype control antibodies (2-4 doses) results in anti-PGT121 ADA induction and low plasma concentrations of PGT121. ADA was associated with poor or absent suppression of SHIV viremia. Notably, ADA within macaque plasma recognised another human bNAb 10E8 but did not bind to the variable domains of PGT121, suggesting that ADA were primarily directed against the constant regions of the human antibodies. These findings have implications for the development of preclinical studies examining multiple infusions of human bNAbs.
引用
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页数:10
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