Intravaginal immunization of mice with recombinant Salmonella enterica serovar Typhimurium expressing human papillomavirus type 16 antigens as a potential route of vaccination against cervical cancer.

Détails

ID Serval
serval:BIB_1010BBF27D4F
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Intravaginal immunization of mice with recombinant Salmonella enterica serovar Typhimurium expressing human papillomavirus type 16 antigens as a potential route of vaccination against cervical cancer.
Périodique
Infection and Immunity
Auteur(s)
Echchannaoui H., Bianchi M., Baud D., Bobst M., Stehle J.C., Nardelli-Haefliger D.
ISSN
1098-5522
Statut éditorial
Publié
Date de publication
2008
Peer-reviewed
Oui
Volume
76
Numéro
5
Pages
1940-1951
Langue
anglais
Notes
Journal Article --- Old month value: May
Résumé
Cervical cancer, the second leading cause of cancer deaths in women, is the consequence of high-risk human papillomavirus (HPV) infections. Toward the development of therapeutic vaccines that can induce both innate and adaptive mucosal immune responses, we analyzed intravaginal (ivag) vaccine delivery of live attenuated Salmonella enterica serovar Typhimurium expressing HPV16L1 as a model antigen. Innate immune responses were examined in cervicovaginal tissues by determining gene expression patterns by microarray analysis using nylon membranes imprinted with cDNA fragments coding for inflammation-associated genes. At 24 h, a wide range of genes, including those for chemokines and Th1- and Th2-type cytokine and chemokine receptors were up-regulated in mice ivag immunized with Salmonella compared to control mice. However, the majority of transcripts returned to their steady-state levels 1 week after immunization, suggesting a transient inflammatory response. Indeed, cervicovaginal histology of immunized mice showed a massive, but transient, infiltration of macrophages and neutrophils, while T cells were still increased after 7 days. Ivag immunization also induced humoral and antitumor immune responses, i.e., serum and vaginal anti-HPV16VLP antibody titers similar to those induced by oral immunization, and significant protection in tumor protection experiments using HPV16-expressing C3 tumor cells. These results show that ivag immunization with live attenuated Salmonella expressing HPV16 antigens modulates the local mucosal gene expression pattern into a transient proinflammatory profile, elicits strong systemic and mucosal immunity against HPV16, and confers protection against HPV16 tumor cells subcutaneously implanted in mice. Examination of the efficacy with which ivag HPV16E7E6 Salmonella induces regression of tumors located in cervicovaginal tissue is warranted.
Mots-clé
Administration, Intravaginal, Animals, Antibodies, Neoplasm, Antibodies, Viral, Capsid Proteins, Cervix Uteri, Cytokines, Female, Gene Expression Profiling, Human papillomavirus 16, Macrophages, Mice, Neoplasms, Neutrophils, Oligonucleotide Array Sequence Analysis, Oncogene Proteins, Viral, Papillomavirus Vaccines, Receptors, Cytokine, Salmonella typhimurium, T-Lymphocytes, Time Factors, Vagina
Pubmed
Web of science
Open Access
Oui
Création de la notice
25/06/2008 11:34
Dernière modification de la notice
20/08/2019 13:36
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