Salmonella enterica serovar Typhi Ty21a expressing human papillomavirus type 16 L1 as a potential live vaccine against cervical cancer and typhoid fever
| Autor: | John T. Schiller, Martine Bobst, Denise Nardelli-Haefliger, Françoise Ponci, Nathalie Zosso, David Baud, Susana Yuk-Ying Pang, Dominique Fraillery |
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| Rok vydání: | 2007 |
| Předmět: |
Microbiology (medical)
Salmonella Ty21a Clinical Biochemistry Immunology Genetic Vectors Uterine Cervical Neoplasms medicine.disease_cause Salmonella typhi Vaccines Attenuated complex mixtures Cancer Vaccines Typhoid fever Microbiology Papillomavirus Vaccines Mice medicine Immunology and Allergy Animals Humans Vaccines Combined Typhoid Fever Cells Cultured Human papillomavirus 16 Mice Inbred BALB C Vaccines Synthetic Attenuated vaccine biology Polysaccharides Bacterial Typhoid-Paratyphoid Vaccines Oncogene Proteins Viral biology.organism_classification medicine.disease Vaccine Research Virology Salmonella enterica Typhoid vaccine Capsid Proteins Female Plasmids |
| Zdroj: | Clinical and vaccine immunology : CVI. 14(10) |
| ISSN: | 1556-6811 |
| Popis: | Human papillomavirus (HPV) vaccines based on L1 virus-like particles (VLPs) can prevent HPV-induced genital neoplasias, the precursors of cervical cancer. However, most cervical cancers occur in developing countries, where the implementation of expensive vaccines requiring multiple injections will be difficult. A live Salmonella -based vaccine could be a lower-cost alternative. We previously demonstrated that high HPV type 16 (HPV16)-neutralizing titers are induced after a single oral immunization of mice with attenuated Salmonella enterica serovar Typhimurium strains expressing a codon-optimized version of HPV16 L1 (L1S). To allow the testing of this type of vaccine in women, we constructed a new L1-expressing plasmid, kanL1S, and tested kanL1S recombinants of three Salmonella enterica serovar Typhi vaccine strains shown to be safe in humans, i.e., Ty21a, the actual licensed typhoid vaccine, and two highly immunogenic typhoid vaccine candidates, Ty800 and CVD908- htrA . In an intranasal mouse model of Salmonella serovar Typhi infection, Ty21a kanL1S was unique in inducing HPV16-neutralizing antibodies in serum and genital secretions, while anti- Salmonella responses were similar to those against the parental Ty21a vaccine. Electron microscopy examination of Ty21a kanL1S lysates showed that L1 assembled in capsomers and capsomer aggregates but not well-ordered VLPs. Comparison to the neutralizing antibody response induced by purified HPV16 L1 VLP immunizations in mice suggests that Ty21a kanL1S may be an effective prophylactic HPV vaccine. Ty21a has been widely used against typhoid fever in humans with a remarkable safety record. These finds encourage clinical testing of Ty21a kanL1S as a combined typhoid fever/cervical cancer vaccine with the potential for worldwide application. |
| Databáze: | OpenAIRE |
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