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VRC01 antibody protects against vaginal and rectal transmission of human immunodeficiency virus 1 in hu-BLT mice

Sun, Ming, Li, Yue, Yuan, Zhe, Lu, Wuxun, Kang, Guobin, Fan, Wenjin, Li, Qingsheng
Archives of virology 2016 v.161 no.9 pp. 2449-2455
Human immunodeficiency virus 1, antiviral agents, bone marrow, immunoglobulin G, liver, mice, neutralizing antibodies, quantitative polymerase chain reaction, reverse transcriptase polymerase chain reaction, thymus gland, vaccine development
Broadly neutralizing antibodies (bNAbs) represent a new generation of antiviral agents for the prevention and treatment of human immunodeficiency virus 1 (HIV-1) infection. A better understanding of the in vivo efficacy of HIV-1 bNAbs, such as VRC01, in preventing mucosal transmission of HIV-1 has important implications for HIV-1 vaccine design. In this study, we evaluated the efficacy of passively transferred VRC01 antibody in preventing HIV-1 vaginal and rectal transmission in humanized bone marrow/liver/thymus mice (hu-BLT mice). Mice were subcutaneously injected with VRC01 IgG, and 24 hours later, they were challenged intravaginally or intrarectally with HIV-1Ada. All hu-BLT mice receiving VRC01 IgG antibody were aviremic at 2 weeks after intravaginal (n = 3) or intrarectal (n = 6) challenge as measured by quantitative real-time RT-PCR. In contrast, mice receiving control IgG all became infected. By 5 and 6 weeks post-challenge, some of VRC01 aviremic mice in both the intravaginal and intrarectal challenge groups became viremic. Our results suggest that VRC01 antibody can be protective against HIV-1 vaginal and rectal transmission; however, a single administration of VRC01 cannot completely prevent mucosal infection.