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Antibody-mediated neutralization of cytomegalovirus: modulation of efficacy induced through the IgG constant region.

In English

Författare

Summary, in English

Antibodies can neutralize the infectious properties of human cytomegalovirus (CMV). In vivo, the major neutralization determinants are located on glycoprotein B (gB). Recombinant human antibodies, that carry different constant regions (IgG1, IgG3 and the synthetic variant IgG3mA) against two of these epitopes were investigated for their ability to recruit the complement cascade for destruction of the virus. It was shown that all variants of an antibody against the antigenic domain (AD)-2 epitope displayed a similar neutralization activity despite the fact that improved C1q binding was observed for IgG3 and IgG3mA over the IgG1 variant. In contrast, an antibody against the AD-1 epitope carrying the normal IgG3 constant region, was less efficient than its IgG1 counterpart in neutralizing the virus in the absence of complement. However, it restored its activity in the presence of complement to the level of the naturally occurring IgG1 version. The same antibody was substantially more potent in neutralizing the virus in the presence of complement if it carried the IgG3mA constant region. This demonstrates the importance of the constant domain for the biological activity of AD-1 specific antibodies, a factor that should be taken into account when using antibody-based therapeutics or when inducing antibodies by vaccination.

Publiceringsår

2002

Språk

Engelska

Sidor

833-840

Publikation/Tidskrift/Serie

Molecular Immunology

Volym

38

Issue

11

Dokumenttyp

Artikel i tidskrift

Förlag

Pergamon Press Ltd.

Ämne

  • Immunology in the medical area

Nyckelord

  • Neutralization Tests
  • Immunoglobulin G : immunology
  • Molecular Sequence Data
  • Immunoglobulin Constant Region : immunology
  • Human
  • Cytomegalovirus : immunology
  • Complement : physiology
  • Base Sequence
  • Viral : immunology
  • Antibodies
  • Recombinant Proteins : immunology
  • Support
  • Non-U.S. Gov't

Status

Published

ISBN/ISSN/Övrigt

  • ISSN: 1872-9142