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一种广泛反应性人源化单克隆抗体KD-247对HIV-1准种的体外中和作用

Ex vivo neutralization of HIV-1 quasi-species by a broadly reactive humanized monoclonal antibody KD-247.

作者信息

Matsushita Shuzo, Takahama Soichiro, Shibata Junji, Kimura Tetsuya, Shiozaki Koichi, Eda Yasuyuki, Koito Atsushi, Murakami Toshio, Yoshimura Kazuhisa

机构信息

Division of Clinical Retrovirology and Infectious Diseases, Center for AIDS Research, Kumamoto University, Japan.

出版信息

Hum Antibodies. 2005;14(3-4):81-8.

Abstract

By immunizing mice sequentially with six different V3 peptides we obtained a murine monoclonal antibody (MAb) C25, and its humanized counterpart KD-247. The MAb recognizes the sequence IGPGRA at the tip of the V3 loop and displays broad neutralizing activity against a variety of HIV-1 isolates. KD-247 was tested in an ex vivo neutralization assay to determine its capability to contain the spread of a quasi species population of clade B HIV-1 derived from two patients. The epitope of KD-247 was generally matching with the V3 sequences of various clones isolated from plasma and peripheral blood mononuclear cells (PBMC) of two patients. Complete or strong inhibition of viral replication was observed when the patients' PBMC were cultured with a high concentration of KD-247. Some neutralization escape variants, which had mutations in the V3 or outside of the V3 loop, emerged only at a low concentration of the MAb. These results suggest that KD-247 could be a good candidate for immunotherapy against HIV-1 in vivo.

摘要

通过用六种不同的V3肽依次免疫小鼠,我们获得了一种鼠单克隆抗体(MAb)C25及其人源化对应物KD-247。该单克隆抗体识别V3环顶端的序列IGPGRA,并对多种HIV-1分离株表现出广泛的中和活性。在体外中和试验中对KD-247进行了测试,以确定其抑制源自两名患者的B亚型HIV-1准种群体传播的能力。KD-247的表位通常与从两名患者的血浆和外周血单核细胞(PBMC)中分离出的各种克隆的V3序列相匹配。当患者的PBMC与高浓度的KD-247一起培养时,观察到病毒复制受到完全或强烈抑制。一些在V3或V3环外发生突变的中和逃逸变体仅在低浓度的单克隆抗体存在时出现。这些结果表明,KD-247可能是体内抗HIV-1免疫治疗的良好候选药物。

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