Immunogenicity against human papillomavirus type 16 virus-like particles is strongly enhanced by the PhoPc phenotype in Salmonella enterica serovar Typhimurium.

Détails

ID Serval
serval:BIB_9073A3E52136
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Immunogenicity against human papillomavirus type 16 virus-like particles is strongly enhanced by the PhoPc phenotype in Salmonella enterica serovar Typhimurium.
Périodique
Infection and Immunity
Auteur(s)
Baud D., Benyacoub J., Revaz V., Kok M., Ponci F., Bobst M., Curtiss R., De Grandi P., Nardelli-Haefliger D.
ISSN
0019-9567 (Print)
ISSN-L
0019-9567
Statut éditorial
Publié
Date de publication
02/2004
Volume
72
Numéro
2
Pages
750-756
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
Recombinant Salmonella strains have been widely used to deliver heterologous antigens and induce immune responses in vaccinated animals and humans. It remains to be established, however, how these bacteria mount an immune response; this has prevented the rational design of vaccines. Here we report for the first time that a particular genetic program, PhoPc, is necessary for recombinant Salmonella strains to induce an antibody response to a heterologous antigen, the human papillomaviruses type 16 (HPV16) virus-like particle (VLP). The PhoPc phenotype results from a point mutation in phoQ, the gene encoding the sensor component of a two-component regulatory system (PhoP-PhoQ) that controls the expression of a number of virulence factors in Salmonellae. To demonstrate that immunogenicity of the viral antigen expressed by the bacterial vector was dependent on the PhoPc phenotype, we have expressed the phoQ mutant gene (phoQ24) in two differently attenuated Salmonella enterica serovar Typhimurium strains. Our data show extrachromosomal phoQ24 to be dominant over the chromosomal copy of the phoQ gene, conferring the PhoPc phenotype on the recipient strains. In addition, activation of PhoPQ-regulated genes by the plasmid-encoded PhoQ24 did not alter bacterial survival and conferred immunogenicity to the HPV16 VLP expressed in the two S. enterica serovar Typhimurium backgrounds, inducing the production of HPV-specific antibodies in mice. This strongly suggests that at least one of the PhoP-regulated genes is necessary for mounting an efficient antibody response to HPV16 VLP. This finding sets the stage for further development of a Salmonella-based vaccine against HPV infection and cervical cancer.
Mots-clé
Animals, Antibodies, Viral/biosynthesis, Bacterial Proteins/genetics, Female, Mice, Mice, Inbred BALB C, Papillomaviridae/immunology, Phenotype, Promoter Regions, Genetic, Salmonella typhimurium/genetics, Salmonella typhimurium/immunology, Vaccines, Synthetic/immunology, Virion/immunology
Pubmed
Web of science
Open Access
Oui
Création de la notice
25/01/2008 16:39
Dernière modification de la notice
08/05/2019 21:58
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