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Postinfection passive transfer of KD-247 protects against simian/human immunodeficiency virus-induced CD4+ T-cell loss in macaque lymphoid tissue

Murakami, Toshioa; Eda, Yasuyukia; Nakasone, Tadashib; Ami, Yasushic; Someya, Kenjid; Yoshino, Naotob; Kaizu, Masahikob; Izumi, Yasuyukib; Matsui, Hajimea; Shinohara, Katsuakie; Yamamoto, Naokib; Honda, Mitsuob

doi: 10.1097/QAD.0b013e32832e5331
Basic Science

Background: Preadministration of high-affinity humanized anti-HIV-1 mAb KD-247 by passive transfer provides sterile protection of monkeys from heterologous chimeric simian/human immunodeficiency virus infection.

Methods: Beginning 1 h, 1 day, or 1 week after simian/human immunodeficiency virus-C2/1 challenge (20 50% tissue culture infective dose), mature, male cynomolgus monkeys received multiple passive transfers of KD-247 (45 mg/kg) on a weekly basis for approximately 2 months. Concentrations and viral loads were measured in peripheral blood, and CD4+ T-cell counts were examined in both peripheral blood and various lymphoid tissues.

Results: Pharmacokinetic examination revealed similar plasma maintenance levels ranging from 200 to 500 μg/ml of KD-247 in the three groups. One of the six monkeys given KD-247 could not maintain these concentrations, and elicitation of anti-KD-247 idiotype antibody was suggested. All monkeys given KD-247 exhibited striking postinfection protection against both CD4+ T-cell loss in various lymphoid tissues and atrophic changes in organs compared with control group animals treated with normal human immunoglobulin G. The KD-247-treated groups were also partially protected against plasma viral load elevation in peripheral blood samples, although the complete protection previously reported with preadministration of this mAb was not achieved.

Conclusion: Postinfection passive transfer of humanized mAb KD-247 with strong neutralizing capacity against challenged virus simian/human immunodeficiency virus-C2/1 protected CD4+ T cells in lymphoid organs.

aThe Chemo-Sero-Therapeutic Research Institute (Kaketsuken), Kyokushi, Kikuchi, Kumamoto, Japan

bAIDS Research Center, Japan

cDivision of Experimental Animal Research, Japan

dDepartment of Virology III, Japan

eDivision of Biosafety Control, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo, Japan.

Received 8 January, 2009

Revised 7 April, 2009

Accepted 18 May, 2009

Correspondence to Toshio Murakami, PhD, The Chemo-Sero-Therapeutic Research Institute (Kaketsuken), Kyokushi, Kikuchi, Kumamoto 869-1298, Japan. Tel: +81 968 37 3172; fax: +81 968 37 3930; e-mail: murakami-tos@kaketsuken.or.jp

© 2009 Lippincott Williams & Wilkins, Inc.