Immunisation of mice using Salmonella typhimurium expressing human papillomavirus type 16 E7 epitopes inserted into hepatitis B virus core antigen

Londono, Laura; Chatfield, Steven N.; Tindle, Robert W.; Herd, Karen A.; Gao, Xuemei; Frazer, Ian H.; Dougan, Gordon

doi:10.1016/0264-410x(95)00216-n

Cited by 60 publications

(1 citation statement)

References 35 publications

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“…The expressed MisL protein included an additional 210 amino acids of its alpha domain to avoid potential protein misfolding in the periplasm and ensure correct conformation in the outer membrane for transit of the passenger domain to the bacterial surface and display of its N-terminus [7,8]. The plasmid used the nirB promoter that is activated under the anaerobic conditions of the intestinal environment and induces improved systemic immune responses towards foreign antigen expressed by orally administered Salmonella vaccine strains [19-21]. This vector is not a high copy number plasmid as antibody responses against antigens delivered by Salmonella are improved when expressed from low to medium copy number plasmids that minimize metabolic stress upon the carrier strain [22,23].…”

Section: Resultsmentioning

confidence: 99%

Improved delivery of the OVA-CD4 peptide to T helper cells by polymeric surface display on Salmonella

et al. 2014

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BackgroundAutotransporter proteins represent a treasure trove for molecular engineers who modify Gram-negative bacteria for the export or secretion of foreign proteins across two membrane barriers. A particularly promising direction is the development of autotransporters as antigen display or secretion systems. Immunologists have been using ovalbumin as a reporter antigen for years and have developed sophisticated tools to detect specific T cells that respond to ovalbumin. Although ovalbumin-expressing bacteria are being used to trace T cell responses to colonizing or invading pathogens, current constructs for ovalbumin presentation have not been optimized.ResultsThe activation of T helper cells in response to ovalbumin was improved by displaying the OVA-CD4 reporter epitope as a multimer on the surface of Salmonella and fused to the autotransporter MisL. Expression was optimized by including tandem in vivo promoters and two post-segregational killing systems for plasmid stabilization.ConclusionsThe use of an autotransporter protein to present relevant epitope repeats on the surface of bacteria, combined with additional techniques favoring stable and efficient in vivo transcription, optimizes antigen presentation to T cells. The technique of multimeric epitope surface display should also benefit the development of new Salmonella or other enterobacterial vaccines.

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Section: Resultsmentioning

confidence: 99%

Improved delivery of the OVA-CD4 peptide to T helper cells by polymeric surface display on Salmonella

et al. 2014

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Cervical cancer vaccines: Emerging concepts and developments

et al. 2001

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Certain human cancers are linked to infection by oncogenic viruses that are able to cause transformation of the normal host cell into a cancerous cell. Human papillomavirus (HPV) DNA and expression of viral transforming proteins are found in virtually all cervical cancer cells, indicating an important role of this virus in the pathogenesis of the disease. Evidence exists that the immune response to cancer cells can play a major role in determining the outcome of disease. The fact that HPV is a necessary cause for cervical cancer provides a clear opportunity to develop a therapeutic vaccine against the virus to treat patients with cervical cancer at its early and late stages. Development of a prophylactic vaccine for HPV would also reduce the incidence of cervical neoplasias by preventing virus infection. Various candidate HPV vaccines are being developed and tested in animal models and/or in human clinical trials. These HPV vaccines, both preventive and therapeutic, are the subjects of this review.

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