Monoclonal antibody therapy for Junin virus infection

被引：45

作者：

Zeitlin, Larry ^{[1
]}

Geisbert, Joan B. ^{[2
,3
]}

Deer, Daniel J. ^{[2
,3
]}

Fenton, Karla A. ^{[2
,3
]}

Bohorov, Ognian ^{[1
]}

Bohorova, Natasha ^{[1
]}

Goodman, Charles ^{[1
]}

Kim, Do ^{[1
]}

Hiatt, Andrew ^{[1
]}

Pauly, Michael H. ^{[1
]}

Velasco, Jesus ^{[1
]}

Whaley, Kevin J. ^{[1
]}

Altmann, Friedrich ^{[4
]}

Gruber, Clemens ^{[4
]}

Steinkellner, Herta ^{[5
]}

Honko, Anna N. ^{[6
,9
]}

Kuehne, Ana I. ^{[6
]}

Aman, M. Javad ^{[7
]}

Sahandi, Sara ^{[7
]}

Enterlein, Sven ^{[7
]}

Zhan, Xiaoguo ^{[7
]}

Enria, Delia ^{[8
]}

Geisbert, Thomas W. ^{[2
,3
]}

机构：

[1] Mapp Biopharmaceut Inc, San Diego, CA 92121 USA

[2] Univ Texas Med Branch, Galveston Natl Lab, Galveston, TX 77555 USA

[3] Univ Texas Med Branch, Dept Microbiol & Immunol, Galveston, TX 77555 USA

[4] Univ Nat Resources & Appl Life Sci, Dept Chem, A-1190 Vienna, Austria

[5] Univ Nat Resources & Appl Life Sci, Dept Appl Genet & Cell Biol, A-1190 Vienna, Austria

[6] US Army Med Res Inst Infect Dis, Virol Div, Frederick, MD 21702 USA

[7] Integrated BioTherapeut Inc, Gaithersburg, MD 20878 USA

[8] Inst Nacl Enfermedades Virales Humanas, Buenos Aires, DF, Argentina

[9] NIAID, Integrated Res Facil, Frederick, MD 21702 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2016年 / 113卷 / 16期

关键词：

Junin; therapy; immunotherapy; hemorrhagic fever; ARGENTINE HEMORRHAGIC-FEVER; GUINEA-PIGS; IMMUNE PLASMA; EFFICACY; DISEASE; IGG; ENCEPHALITIS; PATHOGENESIS; EXPRESSION; MODEL;

D O I：

10.1073/pnas.1600996113

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Countermeasures against potential biothreat agents remain important to US Homeland Security, and many of these pharmaceuticals could have dual use in the improvement of global public health. Junin virus, the causative agent of Argentine hemorrhagic fever (AHF), is an arenavirus identified as a category A high-priority agent. There are no Food and Drug Administration (FDA) approved drugs available for preventing or treating AHF, and the current treatment option is limited to administration of immune plasma. Whereas immune plasma demonstrates the feasibility of passive immunotherapy, it is limited in quantity, variable in quality, and poses safety risks such as transmission of transfusion-borne diseases. In an effort to develop a monoclonal antibody (mAb)-based alternative to plasma, three previously described neutralizing murine mAbs were expressed as mouse-human chimeric antibodies and evaluated in the guinea pig model of AHF. These mAbs provided 100% protection against lethal challenge when administered 2 d after infection (dpi), and one of them(J199) was capable of providing 100% protection when treatment was initiated 6 dpi and 92% protection when initiated 7 dpi. The efficacy of J199 is superior to that previously described for all other evaluated drugs, and its high potency suggests that mAbs like J199 offer an economical alternative to immune plasma and an effective dual use (bioterrorism/public health) therapeutic.

引用

页码：4458 / 4463

页数：6

共 33 条

[1] Therapeutic strategies to improve drug delivery across the blood-brain barrier [J].