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Journal of Virology, September 1999, p. 7565-7573, Vol. 73, No. 9
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Antibody-Dependent and -Independent Protection
following Intranasal Immunization of Mice with Rotavirus
Particles
Monica M.
McNeal,1
Mary N.
Rae,1
Judy A.
Bean,2 and
Richard L.
Ward1,*
Division of Infectious
Diseases1 and Department of
Biostatistics,2 Children's Hospital Medical
Center, Cincinnati, Ohio 45229
Received 12 January 1999/Accepted 25 May 1999
The ability to elicit protective immune responses after intranasal
immunization with rotavirus particles, either with or without the
attenuated Escherichia coli heat-labile enterotoxin
LT(R192G) as an adjuvant, was examined in the adult mouse model. BALB/c mice were administered one or two inoculations of
psoralen/UV-inactivated, triple-layered (tl) or double-layered (dl)
purified rotavirus particles. Four weeks after immunization, mice were
challenged with the murine rotavirus strain EDIM, and the shedding of
rotavirus antigen was quantified. Rotaviruses used for immunization
included EDIM and heterotypic simian (RRV), bovine (WC3), and human
(89-12) strains. tl EDIM stimulated both systemic and intestinal
rotavirus antibody responses and complete protection with as little as
one 1-µg dose. Inclusion of LT(R192G) (10 µg) significantly
increased rotavirus antibody responses and reduced antigen
concentrations needed for full protection. Both dl EDIM and heterotypic
dl and tl particles stimulated protection, but they did so less than tl
EDIM at comparable concentrations, either with or without LT(R192G). When B-cell-deficient µMt mice were immunized with tl EDIM particles, protection was reduced to levels similar to those induced with dl EDIM
and heterotypic particles in BALB/c mice. However, dl EDIM particles
induced similar levels of protection in both mouse strains. The
protection stimulated by tl or dl EDIM particles was not diminished by
CD8 cell depletion prior to immunization in either strain of mice.
These results indicate that tl EDIM induced immunity at least partially
through responses to its outer capsid proteins, presumably by
stimulation of serotype-specific neutralizing antibody. In contrast,
the other particles stimulated protection primarily by an
antibody-independent mechanism. Finally, depletion of CD8 cells had no
effect on protection by either mechanism.
*
Corresponding author. Mailing address: Children's
Hospital Medical Center, Division of Infectious Diseases, 3333 Burnet
Ave., CH-1, Cincinnati, OH 45229-3039. Phone: (513) 636-7628. Fax:
(513) 636-7682. E-mail: wardd0{at}chmcc.org.
Journal of Virology, September 1999, p. 7565-7573, Vol. 73, No. 9
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
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