1887

Abstract

Varicella-zoster virus (VZV), the causative agent of chickenpox and herpes zoster, can be life-threatening in prematurely born children and in children with immune defects or who are under immunosuppressive treatment. Therefore agents for passive immunization, such as VZV-specific immunoglobulin preparations (VZIG) derived from convalescent plasma, are crucial in the prophylaxis of VZV infection. This study describes the isolation of human VZV-neutralizing recombinant antibodies. A human single-chain variable fragment (scFv) phage display library was generated from RNA extracted from peripheral blood lymphocytes of a convalescent varicella patient. Specific phage antibodies were selected against VZV-infected human fibroblasts, and eight unique clones were further expressed as soluble scFv in . They all showed binding characteristics to varicella antigens with affinities in the range 0·1–0·2 μM. Two of the scFv antibodies, VZV4 and VZV5, showed dose-dependent neutralization of VZV. VZV39 also showed a neutralizing effect as scFv, an effect that was increased 4000-fold by conversion into IgG and was further increased by the addition of complement. This is possibly the first time that monovalent scFv antibodies have been shown to neutralize VZV . This finding will have an impact on the production of new prophylactic antibodies, as such antibody fragments can be cost-effectively produced in . The antibodies isolated bind both complement-dependent and -independent epitopes for neutralization, thus they may prove useful tools for the study of VZV virulence mechanisms.

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2004-12-01
2021-10-25
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