VRC01 antibody protects against vaginal and rectal transmission of human immunodeficiency virus 1 in hu-BLT mice
- 415 Downloads
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.
KeywordsHuman Fetal Liver Maximum Percent Inhibition Mucosal Transmission Rectal Transmission VRC01 Antibody
The authors are grateful for the hu-BLT mouse care and maintenance services provided by UNL Life Sciences Annex, and Lance Daharsh for critical reading of this manuscript.
Compliance with ethical standards
This work was supported in part by NIH grant R01 AI111862 (to Li Q. and Guo J.) and NIH P30GM103509. Yue Li was supported by a Fogarty International Center grant at the University of Nebraska-Lincoln (D43 TW001429).
Conflict of interest
The authors declare that they have no conflict of interest.
All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.
- 6.Huang J, Ofek G, Laub L, Louder MK, Doria-Rose NA, Longo NS et al (2012) Broad and potent neutralization of HIV-1 by a gp41-specific human antibody. Nature 491:406–412Google Scholar
- 14.Hessell AJ, Rakasz EG, Tehrani DM, Huber M, Weisgrau KL, Landucci G et al (2010) Broadly neutralizing monoclonal antibodies 2F5 and 4E10 directed against the human immunodeficiency virus type 1 gp41 membrane-proximal external region protect against mucosal challenge by simian-human immunodeficiency virus SHIVBa-L. J Virol 84:1302–1313CrossRefPubMedGoogle Scholar