Cell-surface display of E7 antigen from human papillomavirus type-16 in Lactococcus lactis and in Lactobacillus plantarum using a new cell-wall anchor from lactobacilli.
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.
Cortes-Perez
Naima G
NG
Unité de Recherches Laitières et de Génétique Appliquée, INRA, Domaine de Vilvert, 78352, Jouy-en-Josas, cedex, France.
Azevedo
Vasco
V
Alcocer-González
Juan M
JM
Rodriguez-Padilla
Cristina
C
Tamez-Guerra
Reyes S
RS
Corthier
Gérard
G
Gruss
Alexandra
A
Langella
Philippe
P
Bermúdez-Humarán
Luis G
LG
D000942:Antigens, Bacterial / Q000235:genetics; D000954:Antigens, Surface / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics; D002473:Cell Wall / Q000378:metabolism; D003001:Cloning, Molecular; D005260:Female; D006801:Humans; D048191:Lactiplantibacillus plantarum / Q000235:genetics / Q000378:metabolism*; D013294:Lactococcus lactis / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D027383:Papillomaviridae / Q000235:genetics / Q000276:immunology*; D050725:Papillomavirus E7 Proteins; D011401:Promoter Regions, Genetic; D021382:Protein Sorting Signals; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D013297:Streptococcus pyogenes / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000276:immunology / Q000517:prevention & control
D000942:Antigens, Bacterial; D000954:Antigens, Surface; D000956:Antigens, Viral; D001425:Bacterial Outer Membrane Proteins; D002352:Carrier Proteins; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D021382:Protein Sorting Signals; D011993:Recombinant Fusion Proteins; C059731:oncogene protein E7, Human papillomavirus type 16; C014689:streptococcal M protein