Abstract
The human papillomavirus type-16 (HPV-16) E7 protein is considered a major viral oncoprotein involved in cervical cancer (CxCa) and a potential candidate for the development of a vaccine against this neoplasia. Here, two lactic acid bacteria (the model one Lactococcus lactis and a probiotic one Lactobacillus plantarum) were engineered to deliver an E7 mutant protein (E7mm), which has a reduced transforming activity and consequently, could fit better to therapeutic use in humans than the native form of E7. An efficient cell-surface display of E7mm was obtained in L. lactis using an expression cassette encoding a precursor composed of (i) the signal peptide and the first 15 amino acids of the mature part of the lactococcal Usp45 protein; (ii) E7mm and (iii) the cell-wall anchor of the Streptococcus pyogenes M6 protein (CWA(M6)). This hybrid precursor was produced but not cell-wall anchored in Lb. plantarum. We thus replaced CWA(M6) by the cell-wall anchor of a Lb. plantarum protein which allows an efficient cell-wall anchoring of E7mm in this bacterium. The E7mm production and cell-surface display in both L. lactis and a probiotic bacterium, Lb. plantarum, represent one more step towards the development of a safe and effective treatment against CxCa.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antigens, Bacterial / genetics
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Antigens, Surface / genetics
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Antigens, Surface / immunology
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Antigens, Surface / metabolism
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Antigens, Viral / genetics
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Antigens, Viral / immunology
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Antigens, Viral / metabolism*
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Bacterial Outer Membrane Proteins / genetics
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Base Sequence
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Carrier Proteins / genetics
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Cell Wall / metabolism
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Cloning, Molecular
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Female
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Humans
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Lactobacillus plantarum / genetics
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Lactobacillus plantarum / metabolism*
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Lactococcus lactis / genetics
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Lactococcus lactis / metabolism*
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Molecular Sequence Data
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Oncogene Proteins, Viral / genetics
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Oncogene Proteins, Viral / immunology
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Oncogene Proteins, Viral / metabolism*
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Papillomaviridae / genetics
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Papillomaviridae / immunology*
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Papillomavirus E7 Proteins
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Promoter Regions, Genetic
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Protein Sorting Signals
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / immunology
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Recombinant Fusion Proteins / metabolism*
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Streptococcus pyogenes / metabolism
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Uterine Cervical Neoplasms / immunology
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Uterine Cervical Neoplasms / prevention & control
Substances
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Antigens, Bacterial
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Antigens, Surface
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Antigens, Viral
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Bacterial Outer Membrane Proteins
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Carrier Proteins
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Oncogene Proteins, Viral
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Papillomavirus E7 Proteins
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Protein Sorting Signals
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Recombinant Fusion Proteins
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oncogene protein E7, Human papillomavirus type 16
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streptococcal M protein