Multimeric humanized varicella-zoster virus antibody fragments to gH neutralize virus while monomeric fragments do not

P D Drew; M T Moss; T J Pasieka; C Grose; W J Harris; A J R Porter

doi:10.1099/0022-1317-82-8-1959

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Multimeric humanized varicella-zoster virus antibody fragments to gH neutralize virus while monomeric fragments do not

Journal article

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Peer reviewed

Multimeric humanized varicella-zoster virus antibody fragments to gH neutralize virus while monomeric fragments do not

P D Drew, M T Moss, T J Pasieka, C Grose, W J Harris and A J R Porter

Journal of general virology, Vol.82(Pt 8), pp.1959-1963

08/2001

DOI: 10.1099/0022-1317-82-8-1959

PMID: 11458003

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Abstract

Murine monoclonal antibody 206 (MAb mu206) binds to gH, the varicella-zoster virus (VZV) fusogen, neutralizing the virus in vitro in the absence of complement and inhibiting cell-to-cell spread and egress of VZV in cultured cells. We have humanized this antibody to generate MAb hu206 by complementarity determining region grafting. MAb hu206 retained binding and in vitro neutralizing activity, as well as cross-reactivity with ten different VZV strains. Single-chain antibody fragments (scAb) derived from MAb hu206 were produced in Escherichia coli. These scAb retained the binding properties of the whole antibody. However, monomeric scAb exhibited markedly reduced neutralizing activity compared to the bivalent parental MAb hu206. Shortening the peptide linker joining the V(H) to the V(kappa) domain from 14 to 5 or even 0 residues encouraged multimerization and increased neutralizing efficacy. The fact that Fab fragments enzymatically generated from whole MAb hu206 lost their neutralizing potency lent support to the proposal that valency is important for VZV neutralization at this epitope.

Antibodies, Viral - biosynthesis

Cell Line

Herpes Zoster - immunology

Dose-Response Relationship, Immunologic

Humans

Herpesvirus 3, Human - immunology

Neutralization Tests

Glycoproteins - immunology

Animals

Escherichia coli - genetics

Protein Engineering

Antibodies, Viral - immunology

Viral Envelope Proteins - immunology

Mice

Immunoglobulin Fab Fragments - immunology

Genetic Vectors

Herpesvirus 3, Human - chemistry

Antibodies, Monoclonal - immunology

Antibodies, Viral - genetics

Details

Title: Subtitle: Multimeric humanized varicella-zoster virus antibody fragments to gH neutralize virus while monomeric fragments do not
Creators: P D Drew - University of Aberdeen, Department of Molecular and Cell Biology, Institute of Medical Sciences, Foresterhill, Aberdeen AB25 2ZD, UK1
M T Moss - Scotgen Biopharmaceuticals Inc., Kettock Lodge, Aberdeen Science and Technology Park, Aberdeen AB22 8GU, UK3
T J Pasieka - Department of Microbiology, University of Iowa College of Medicine, Iowa City, IA 52242, USA2
C Grose - Department of Microbiology, University of Iowa College of Medicine, Iowa City, IA 52242, USA2
W J Harris - University of Aberdeen, Department of Molecular and Cell Biology, Institute of Medical Sciences, Foresterhill, Aberdeen AB25 2ZD, UK1
A J R Porter - University of Aberdeen, Department of Molecular and Cell Biology, Institute of Medical Sciences, Foresterhill, Aberdeen AB25 2ZD, UK1
Resource Type: Journal article
Publication Details: Journal of general virology, Vol.82(Pt 8), pp.1959-1963
DOI: 10.1099/0022-1317-82-8-1959
PMID: 11458003
NLM abbreviation: J Gen Virol
ISSN: 0022-1317
eISSN: 1465-2099
Grant note: AI22795 / NIAID NIH HHS AI36884 / NIAID NIH HHS
Language: English
Date published: 08/2001
Academic Unit: Stead Family Department of Pediatrics; Infectious Disease (Pediatrics)
Record Identifier: 9984093221902771

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