Protection against SHIV Challenge by Subcutaneous Administration of the Plant-Derived PGT121 Broadly Neutralizing Antibody in Macaques.
Protection against SHIV Challenge by Subcutaneous Administration of the Plant-Derived PGT121 Broadly Neutralizing Antibody in Macaques.
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DOI：
10.1371/journal.pone.0152760
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Jiang X
中科院分区：
文献类型：
--
作者：
Rosenberg YJ;Montefiori DC;LaBranche CC;Lewis MG;Sack M;Lees JP;Jiang X
广泛中和抗体（bnAb）的血管内递送已经显示出预防和治疗HIV感染的前景。然而，在医疗可及性差的地理位置进行多次IV给药具有实际局限性。我们使用严格的SHIV-SF 162 P3猕猴保护模型评估了皮下（SC）递送的植物来源的PGT 121对阴道内攻击前后的功效。SC给予的PGT 121表现出比IV给予更长的血清半衰期，并且比肌内递送更一致。3.5mg/kg剂量的PGT 121以1：295的最小ID 50中和滴度预防感染，而5 mg/kg剂量在攻毒后立即给药时保护了6只猕猴中的5只。这些结果表明了SC递送的植物来源的bnAb用于HIV预防的效用。
Intravascular delivery of broadly neutralizing antibodies (bnAbs) has shown promise for prevention and treatment of HIV infection. However, multiple IV administrations in geographic locations with poor accessibility to medical care have practical limitations. We have assessed the efficacy of plant-derived PGT121 delivered subcutaneously (SC) against pre-and post-intravaginal challenge using a rigorous SHIV-SF162P3 macaque protection model. SC administered PGT121 exhibited a longer serum half-life than IV administration and was more consistent than intramuscular delivery. A dose of 3.5mg/kg PGT121 prevented infection at a minimum ID50 neutralization titer of 1:295 while 5mg/kg protected five of six macaques when delivered immediately post-challenge. These results suggest the utility of plant-derived bnAbs delivered SC for HIV prevention.