This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Eda, Y. Articles by Honda, M. Search for Related Content PubMed PubMed Citation Articles by Eda, Y. Articles by Honda, M.

 Previous Article  |  Next Article 

Journal of Virology, June 2006, p. 5563-5570, Vol. 80, No. 11
0022-538X/06/$08.00+0     doi:10.1128/JVI.02095-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Anti-V3 Humanized Antibody KD-247 Effectively Suppresses Ex Vivo Generation of Human Immunodeficiency Virus Type 1 and Affords Sterile Protection of Monkeys against a Heterologous Simian/Human Immunodeficiency Virus Infection

The Chemo-Sero-Therapeutic Research Institute, Kyokushi, Kikuchi, Kumamoto 869-1298, Japan,¹ Division of Experimental Animal Research,² AIDS Research Center,³ Division of Biosafety Control, Department of Safety Research on Biologics, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo 162-8640, Japan,⁵ Center for AIDS Research, Kumamoto University, Kumamoto 860-0811, Japan,⁴ Institute of Viral Research, Kyoto University, Kyoto 606-8507, Japan⁶

Received 5 October 2005/ Accepted 9 March 2006

In an accompanying report (Y. Eda, M. Takizawa, T. Murakami, H. Maeda, K. Kimachi, H. Yonemura, S. Koyanagi, K. Shiosaki, H. Higuchi, K. Makizumi, T. Nakashima, K. Osatomi, S. Tokiyoshi, S. Matsushita, N. Yamamoto, and M. Honda, J. Virol. 80:5552-5562, 2006), we discuss our production of a high-affinity humanized monoclonal antibody, KD-247, by sequential immunization with V3 peptides derived from human immunodeficiency virus type 1 (HIV-1) clade B primary isolates. Epitope mapping revealed that KD-247 recognized the Pro-Gly-Arg V3 tip sequence conserved in HIV-1 clade B isolates. In this study, we further demonstrate that in vitro, KD-247 efficiently neutralizes CXCR4- and CCR5-tropic primary HIV-1 clade B and clade B' with matching neutralization sequence motifs but does not neutralize sequence-mismatched clade B and clade E isolates. Monkeys were provided sterile protection against heterologous simian/human immunodeficiency virus challenge by the passive transfer of a single high dose (45 mg per kg of body weight) of KD-247 and afforded partial protection by lower antibody doses (30 and 15 mg per kg). Protective neutralization endpoint titers in plasma at the time of virus challenge were 1:160 in animals passively transferred with a high dose of the antibody. The antiviral efficacy of the antibody was further confirmed by its suppression of the ex vivo generation of primary HIV-1 quasispecies in peripheral blood mononuclear cell cultures from HIV-infected individuals. Therefore, KD-247 promises to be a valuable tool not only as a passive immunization antibody for the prevention of HIV infection but also as an immunotherapy for the suppression of HIV in phenotype-matched HIV-infected individuals.

This article has been cited by other articles:

• Shibata, J., Yoshimura, K., Honda, A., Koito, A., Murakami, T., Matsushita, S. (2007). Impact of V2 Mutations on Escape from a Potent Neutralizing Anti-V3 Monoclonal Antibody during In Vitro Selection of a Primary Human Immunodeficiency Virus Type 1 Isolate. J. Virol. 81: 3757-3768 [Abstract] [Full Text]  
• Eda, Y., Takizawa, M., Murakami, T., Maeda, H., Kimachi, K., Yonemura, H., Koyanagi, S., Shiosaki, K., Higuchi, H., Makizumi, K., Nakashima, T., Osatomi, K., Tokiyoshi, S., Matsushita, S., Yamamoto, N., Honda, M. (2006). Sequential Immunization with V3 Peptides from Primary Human Immunodeficiency Virus Type 1 Produces Cross-Neutralizing Antibodies against Primary Isolates with a Matching Narrow-Neutralization Sequence Motif.. J. Virol. 80: 5552-5562 [Abstract] [Full Text]