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Journal of Virology, July 2000, p. 6132-6146, Vol. 74, No. 13
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Dense Bodies of Human Cytomegalovirus Induce both
Humoral and Cellular Immune Responses in the Absence of Viral
Gene Expression
Sandra
Pepperl,1
Jürgen
Münster,1
Michael
Mach,2
J. Robin
Harris,3 and
Bodo
Plachter1,*
Institute for
Virology1 and Institute for
Zoology,3 University of Mainz, Mainz, and
Institute for Clinical and Molecular Virology, University
of Erlangen-Nürnberg, Erlangen,2 Germany
Received 14 March 2000/Accepted 10 April 2000
Infection of fibroblast cell cultures with human cytomegalovirus
(HCMV) leads to the production of significant amounts of defective
enveloped particles, termed dense bodies (DB). These noninfectious
structures contain major antigenic determinants which are responsible
for induction of both the humoral and the cellular immune response
against HCMV. We tested the hypothesis that, by virtue of their unique
antigenic and structural properties, DB could induce a significant
immune response in the absence of infectious virus. Mice were immunized
with gradient-purified DB, which were either left untreated or
subjected to sequential rounds of sonication and freeze-thawing to
prevent cellular entry. Titers of neutralizing antibodies induced by DB
were in a range comparable to levels present in convalescent human
sera. The virus-neutralizing antibody response was surprisingly
durable, with neutralizing antibodies detected 12 months following
primary immunization. The HCMV-specific major histocompatibility
complex class I-restricted cytolytic T-cell (CTL) response was assayed
using mice transgenic for the human HLA-A2 molecule. Immunization with
DB led to high levels of HCMV-specific CTL in the absence of de novo
viral protein synthesis. Maximal total cytolytic activity in mice
immunized with DB was nearly as efficient as the cytolytic activity
induced by a standard immunization with murine cytomegalovirus.
Furthermore, DB induced a typical T-helper 1 (Th1)-dominated immune
response in mice, as determined by cytokine and immunoglobulin G
isotype analysis. Induction of humoral and cellular immune responses
was achieved without the concomitant use of adjuvant. We thus propose that DB can serve as a basis for the future development of a
recombinant nonreplicating vaccine against HCMV. Finally, such
particles could be engineered for efficient delivery of antigens from
other pathogens to the immune system.
*
Corresponding author. Mailing address: Institut
für Virologie, Johannes Gutenberg-Universität Mainz,
Obere Zahlbacher Str. 67, 55101 Mainz, Germany. Phone:
(49)-6131-3933652. Fax: (49)-6131-3935604. E-mail:
plachter{at}mail.uni-mainz.de.
Journal of Virology, July 2000, p. 6132-6146, Vol. 74, No. 13
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
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