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Infection and Immunity, July 1999, p. 3674-3679, Vol. 67, No. 7
Department of Gynecology,
Received 28 December 1998/Returned for modification 9 March
1999/Accepted 26 April 1999
We have recently shown by using a recombinant Salmonella
typhimurium PhoPc strain in mice the feasibility of
using a Salmonella-based vaccine to prevent infection by
the genital human papillomavirus type 16 (HPV16). Here, we compare the
HPV16-specific antibody responses elicited by nasal immunization with
recombinant S. typhimurium strains harboring attenuations
that, in contrast to PhoPc, are suitable for human use. For
this purpose,
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
The Nature of the Attenuation of Salmonella
typhimurium Strains Expressing Human Papillomavirus Type 16 Virus-Like Particles Determines the Systemic and Mucosal Antibody
Responses in Nasally Immunized Mice
4989 (
cya
crp) and
4990
[
cya
(crp-cdt)] were constructed in the
ATCC 14028 genetic background, and comparison was made with the
isogenic PhoPc and PhoP
strains. Although the
levels of expression of HPV16 virus-like particle (VLP) were similar in
all strains, only PhoPc HPV16 induced sustained specific
antibody responses after nasal immunization, while all strains induced
high antibody responses with a single nasal immunization when an
unrelated viral hepatitis B core antigen was expressed. The level of
the specific antibody responses induced did not correlate with the
number of recombinant bacteria surviving in various organs 2 weeks
after immunization. Our data suggest that the immunogenicity of
attenuated Salmonella vaccine strains does not correlate
with either the number of persisting bacteria after immunization or the
levels of in vitro expression of the antigen carried. Rather, the
PhoPc phenotype appears to provide the unique ability in
Salmonella to induce immune responses against HPV16 VLPs.
*
Corresponding author. Mailing address:
Département de Gynécologie, c/o Institut de Microbiologie,
Bugnon 44, 1011 Lausanne, Switzerland. Phone: 021/314 40 81. Fax:
021/314 40 95. E-mail: DNARDELL{at}hola.hospvd.ch.
Infection and Immunity, July 1999, p. 3674-3679, Vol. 67, No. 7
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
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