Early antibody therapy can induce long-lasting immunity to SHIV

Article

关键词: BROADLY NEUTRALIZING ANTIBODIES;    SIMIAN/HUMAN IMMUNODEFICIENCY VIRUS;    ACTIVE ANTIRETROVIRAL THERAPY;    PRIMARY HIV-1 INFECTION;    CD4(+) T-CELLS;    MONOCLONAL-ANTIBODIES;    HUMANIZED MICE;    RHESUS-MONKEYS;    IN-VIVO;    MACAQUES;   

DOI  :  10.1038/nature21435

来源: SCIE

【 摘 要 】

Highly potent and broadly neutralizing anti-HIV-1 antibodies (bNAbs) have been used to prevent and treat lentivirus infections in humanized mice, macaques, and humans(1-12). In immunotherapy experiments, administration of bNAbs to chronically infected animals transiently suppresses virus replication, which invariably returns to pre-treatment levels and results in progression to clinical disease. Here we show that early administration of bNAbs in a macaque simian/human immunodeficiency virus (SHIV) model is associated with very low levels of persistent viraemia, which leads to the establishment of T-cell immunity and resultant longterm infection control. Animals challenged with SHIVAD8-EO by mucosal or intravenous routes received a single 2-week course of two potent passively transferred bNAbs (3BNC117 and 10-1074 (refs 13, 14)). Viraemia remained undetectable for 56-177 days, depending on bNAb half-life in vivo. Moreover, in the 13 treated monkeys, plasma virus loads subsequently declined to undetectable levels in 6 controller macaques. Four additional animals maintained their counts of T cells carrying the CD4 antigen (CD4+) and very low levels of viraemia persisted for over 2 years. The frequency of cells carrying replication-competent virus was less than 1 per 106 circulating CD4(+) T cells in the six controller macaques. Infusion of a T-cell-depleting anti-CD8 beta monoclonal antibody to the controller animals led to a specific decline in levels of CD8(+) T cells and the rapid reappearance of plasma viraemia. In contrast, macaques treated for 15 weeks with combination anti-retroviral therapy, beginning on day 3 after infection, experienced sustained rebound plasma viraemia when treatment was interrupted. Our results show that passive immunotherapy during acute SHIV infection differs from combination anti-retroviral therapy in that it facilitates the emergence of potent CD8(+) T-cell immunity able to durably suppress virus replication.

【 授权许可】

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