Protection of Humanized Mice From Repeated Intravaginal HIV Challenge by Passive Immunization: A Model for Studying the Efficacy of Neutralizing Antibodies In Vivo

被引:33
作者
Deruaz, Maud [1 ]
Moldt, Brian [3 ,4 ]
Le, Khoa M. [3 ,4 ]
Power, Karen A. [2 ]
Vrbanac, Vladimir D. [1 ,2 ]
Tanno, Serah [1 ,2 ]
Ghehremichael, Musie S. [2 ]
Allen, Todd M. [2 ]
Tager, Andrew M. [1 ,2 ]
Burton, Dennis R. [2 ,3 ,4 ]
Luster, Andrew D. [1 ]
机构
[1] Harvard Med Sch, Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Ctr Immunol & Inflammatory Dis, Boston, MA USA
[2] Ragon Inst MGH MIT & Harvard, Cambridge, MA USA
[3] Scripps Res Inst, Ctr HIV AIDS Vaccine Immunol & Immunogen Discover, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA
[4] Scripps Res Inst, IAVI Neutralizing Antibody Ctr, La Jolla, CA 92037 USA
基金
美国国家卫生研究院;
关键词
humanized mice; neutralizing antibodies; HIV transmission; mucosal infection; MUCOSAL SHIV CHALLENGE; MONOCLONAL-ANTIBODY; MOUSE MODEL; BLT MICE; TRANSMISSION; THERAPY;
D O I
10.1093/infdis/jiw203
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Humanized mice reconstituted with a human immune system can be mucosally infected with human immunodeficiency virus (HIV), opening up the possibility of studying HIV transmission in a small-animal model. Here we report that passive immunization with the broadly neutralizing antibody b12 protected humanized mice against repetitive intravaginal infection in a dose-dependent manner. In addition, treatment with the antibody PGT126, which is more potent in vitro, was more efficacious in vivo and provided sterilizing protection. Our results demonstrate that humanized mice can be used as a small-animal model to study the efficacy and mechanism of broadly neutralizing antibody protection against HIV acquisition.
引用
收藏
页码:612 / 616
页数:5
相关论文
共 15 条
[1]   Vectored immunoprophylaxis protects humanized mice from mucosal HIV transmission [J].
Balazs, Alejandro B. ;
Ouyang, Yong ;
Hong, Christin M. ;
Chen, Joyce ;
Nguyen, Steven M. ;
Rao, Dinesh S. ;
An, Dong Sung ;
Baltimore, David .
NATURE MEDICINE, 2014, 20 (03) :296-300
[2]   Broadly Neutralizing Anti-HIV-1 Antibodies Require Fc Effector Functions for In Vivo Activity [J].
Bournazos, Stylianos ;
Klein, Florian ;
Pietzsch, John ;
Seaman, Michael S. ;
Nussenzweig, Michel C. ;
Ravetch, Jeffrey V. .
CELL, 2014, 158 (06) :1243-1253
[3]   Induction of Robust Cellular and Humoral Virus-Specific Adaptive Immune Responses in Human Immunodeficiency Virus-Infected Humanized BLT Mice [J].
Brainard, Diana M. ;
Seung, Edward ;
Frahm, Nicole ;
Cariappa, Annaiah ;
Bailey, Charles C. ;
Hart, William K. ;
Shin, Hae-Sook ;
Brooks, Sarah F. ;
Knight, Heather L. ;
Eichbaum, Quentin ;
Yang, Yong-Guang ;
Sykes, Megan ;
Walker, Bruce D. ;
Freeman, Gordon J. ;
Pillai, Shiv ;
Westmoreland, Susan V. ;
Brander, Christian ;
Luster, Andrew D. ;
Tager, Andrew M. .
JOURNAL OF VIROLOGY, 2009, 83 (14) :7305-7321
[4]   EFFICIENT NEUTRALIZATION OF PRIMARY ISOLATES OF HIV-1 BY A RECOMBINANT HUMAN MONOCLONAL-ANTIBODY [J].
BURTON, DR ;
PYATI, J ;
KODURI, R ;
SHARP, SJ ;
THORNTON, GB ;
PARREN, PWHI ;
SAWYER, LSW ;
HENDRY, RM ;
DUNLOP, N ;
NARA, PL ;
LAMACCHIA, M ;
GARRATTY, E ;
STIEHM, ER ;
BRYSON, YJ ;
CAO, YZ ;
MOORE, JP ;
HO, DD ;
BARBAS, CF .
SCIENCE, 1994, 266 (5187) :1024-1027
[5]   Viraemia suppressed in HIV-1-infected humans by broadly neutralizing antibody 3BNC117 [J].
Caskey, Marina ;
Klein, Florian ;
Lorenzi, Julio C. C. ;
Seaman, Michael S. ;
West, Anthony P., Jr. ;
Buckley, Noreen ;
Kremer, Gisela ;
Nogueira, Lilian ;
Braunschweig, Malte ;
Scheid, Johannes F. ;
Horwitz, Joshua A. ;
Shimeliovich, Irina ;
Ben-Avraham, Sivan ;
Witmer-Pack, Maggi ;
Platten, Martin ;
Lehmann, Clara ;
Burke, Leah A. ;
Hawthorne, Thomas ;
Gorelick, Robert J. ;
Walker, Bruce D. ;
Keler, Tibor ;
Gulick, Roy M. ;
Faetkenheuer, Gerd ;
Schlesinger, Sarah J. ;
Nussenzweig, Michel C. .
NATURE, 2015, 522 (7557) :487-+
[6]   Antiretroviral pre-exposure prophylaxis prevents vaginal transmission of HIV-1 in humanized BLT mice [J].
Denton, Paul W. ;
Estes, Jacob D. ;
Sun, Zhifeng ;
Othieno, Florence A. ;
Wei, Bangdong L. ;
Wege, Anja K. ;
Powell, Daniel A. ;
Payne, Deborah ;
Haase, Ashley T. ;
Garcia, J. Victor .
PLOS MEDICINE, 2008, 5 (01) :79-89
[7]   Antibody and Antiretroviral Preexposure Prophylaxis Prevent Cervicovaginal HIV-1 Infection in a Transgenic Mouse Model [J].
Gruell, Henning ;
Bournazos, Stylianos ;
Ravetch, Jeffrey V. ;
Ploss, Alexander ;
Nussenzweig, Michel C. ;
Pietzsch, John .
JOURNAL OF VIROLOGY, 2013, 87 (15) :8535-8544
[8]   Effective, low-titer antibody protection against low-dose repeated mucosal SHIV challenge in macaques [J].
Hessell, Ann J. ;
Poignard, Pascal ;
Hunter, Meredith ;
Hangartner, Lars ;
Tehrani, David M. ;
Bleeker, Wim K. ;
Parren, Paul W. H. I. ;
Marx, Preston A. ;
Burton, Dennis R. .
NATURE MEDICINE, 2009, 15 (08) :951-U155
[9]   Inhibitory effect of HIV-specific neutralizing IgA on mucosal transmission of HIV in humanized mice [J].
Hur, Eun Mi ;
Patel, Sonal N. ;
Shimizu, Saki ;
Rao, Dinesh S. ;
Gnanapragasam, Priyanthi N. P. ;
An, Dong Sung ;
Yang, Lili ;
Baltimore, David .
BLOOD, 2012, 120 (23) :4571-4582
[10]   Antibodies in HIV-1 Vaccine Development and Therapy [J].
Klein, Florian ;
Mouquet, Hugo ;
Dosenovic, Pia ;
Scheid, Johannes F. ;
Scharf, Louise ;
Nussenzweig, Michel C. .
SCIENCE, 2013, 341 (6151) :1199-1204