Nakamura M, Armour K, Terada M, Carr FJ, Ohno T, Harris WJ; International Conference on AIDS.
Int Conf AIDS. 1994 Aug 7-12; 10: 86 (abstract no. PA0223).
Jikei University School of Medicine, Tokyo, Japan.
OBJECTIVE: Murine monoclonal antibody NM-01 has been shown previously to neutralize a broad range of isolates of HIV in vitro and also to induce complement dependent lysis of HIV particles. We have humanised NM01 with the aim of retaining full biological activity within a human IgG1 in preparation for clinical studies. METHODS: The heavy and light variable immunoglobulin genes from NM01 were cloned and sequenced and the CDR's transferred into human IgG1 immunoglobulin constructs and transfected into mouse NSO cells for expression. Strategic changes were made in human frameworks to restore antigen binding affinity. In vitro neutralization assays were carried out by measuring both reverse transcriptase and p24 levels and syncytium formation. Virolysis was confirmed by electron microscopy and flow cytometry analysis. RESULTS AND DISCUSSION: Humanised hNM01 was at least as effective as the original murine antibody in neutralizing MN and IIIB strains of HIV by all assays studied and was several fold more potent at neutralization in the presence of human complement. Neutralization studies of clinical isolates are in progress and will be reported.
Publication Types:
Keywords:
- AIDS Vaccines
- Acquired Immunodeficiency Syndrome
- Animals
- Anti-HIV Agents
- Antibodies, Monoclonal
- Complement System Proteins
- Complementarity Determining Regions
- Flow Cytometry
- HIV
- HIV Antibodies
- HIV Antigens
- HIV Core Protein p24
- HIV Envelope Protein gp120
- HIV Infections
- HIV Seropositivity
- Humans
- Immunoglobulin G
- In Vitro
- Mice
- immunology
Other ID:
UI: 102211351
From Meeting Abstracts