Polyclonal cytomegalovirus-specific antibodies not only prevent virus dissemination from the portal of entry but also inhibit focal virus spread within target tissues.
Therapy of cytomegalovirus (CMV) infection in recipients of hematopoietic stem cell transplantation (HSCT) by immune serum transfer did not fulfill the high clinical expectations, although immune sera or immunoglobulin-enriched preparations pooled from many CMV-immune donors are likely to contain virus neutralizing antibodies covering a broad range of virus variants. Likewise, the highest risk of CMV disease in HSCT recipients results from the reactivation of the latently infected recipient's own virus despite pre-transplantation humoral immunity. These findings suggest the conclusion that antiviral antibodies are inefficient in controlling CMV. Rather than B cells and antibodies, T cells, in particular CD8 T cells, are thought to play a major role in resolving established organ infection. In theory, antibodies, though being capable of neutralizing free virions, could fail to prevent cell-bound virus dissemination from the portal of entry to distant target tissues and also could fail in preventing cell-to-cell spread within tissue. Here we have used murine model systems, including B cell deficient C57BL/6 micro(- ) micro(-) (microMT) mutants, to revisit the role of antiviral antibodies in the control of CMV infection and to reevaluate the prospects of an antibody-based immunotherapy from a basic science point of view.
Wirtz
Nikolaus
N
Institute for Virology, Johannes Gutenberg-University, Obere Zahlbacher Strasse 67, Hochhaus am Augustusplatz, 55131 Mainz, Germany.
Schader
Sina I
SI
Holtappels
Rafaela
R
Simon
Christian O
CO
Lemmermann
Niels A W
NA
Reddehase
Matthias J
MJ
Podlech
Jürgen
J
D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D003587:Cytomegalovirus / Q000276:immunology*; D016867:Immunocompromised Host; D008099:Liver / Q000276:immunology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009500:Neutralization Tests
D000914:Antibodies, Viral