title: Transgenic tobacco expressed HPV16-L1 and LT-B combined immunization induces strong mucosal and systemic immune responses in mice.
abstract: BACKGROUND
  Although there are two HPV vaccines have been used to prevent cervical cancer, the cost limits their application in developing countries. The aim of this study was to evaluate the potential value of plant-based HPV16L1 and LTB proteins as a high-efficiency, low-cost and easy-to-use HPV16L1 oral vaccine.
  
  
  RESULTS
  Transgenic plant-derived HPV16L1 and LTB were identified, which display potent immunogenicity and biologic activity. Higher levels of specific IgG and IgA levels of HPV16L1 were induced when mice were immunized with L1 combined with LTB by the oral route. The stimulation index (SI) of spleen cells from the L1/LTB-immunized group was significantly higher than that in the L1-immunized group (p < 0.05). The percentage of IFN-γ (+) /IL-4 (+) CD4 (+) T cells from the L1/LTB group was clearly increased compared with that in the L1 and control groups (p < 0.05).
  
  
  METHODS
  Plant-expressed HPV16L1 and LTB proteins were extracted from transgenic tobacco leaves, and their biologic characteristics and activity were examined with electron microscopy and GM1-binding assays respectively. Mice were immunized orally with either HPV16L1 or LTB alone or in combination. Induced mucosal and systemic immune responses were detected by ELISA, Hemagglutination inhibition (HAI), lymphocyte proliferation assays and flow cytometry analysis.
  
  
  CONCLUSIONS
  Strong mucosal and systemic immune responses were induced by transgenic tobacco derived HPV16-L1 and LTB combined immunization. This study will lay the foundation for the development of a new type of vaccine to decrease HPV16 infections, which may lead to the prevention of cervical cancer.
authors.affiliation: First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi Province, PR China.
authors.forename: Liu
authors.initials: L
authors.lastname: Hongli
authors.forename: Li
authors.initials: L
authors.lastname: Xukui
authors.forename: Lei
authors.initials: L
authors.lastname: Ting
authors.forename: Li
authors.initials: L
authors.lastname: Wensheng
authors.forename: Si
authors.initials: S
authors.lastname: Lusheng
authors.forename: Zheng
authors.initials: Z
authors.lastname: Jin
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000235:genetics / Q000302:isolation & purification; D000284:Administration, Oral; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D001427:Bacterial Toxins / Q000008:administration & dosage* / Q000235:genetics / Q000302:isolation & purification; D036022:Capsid Proteins / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D049109:Cell Proliferation; D004768:Enterotoxins / Q000008:administration & dosage* / Q000235:genetics / Q000302:isolation & purification; D029968:Escherichia coli Proteins / Q000008:administration & dosage* / Q000235:genetics / Q000302:isolation & purification; D005260:Female; D005434:Flow Cytometry; D018928:Immunity, Mucosal; D007070:Immunoglobulin A / Q000032:analysis; D007074:Immunoglobulin G / Q000032:analysis / Q000097:blood; D007371:Interferon-gamma / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D053918:Papillomavirus Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D030821:Plants, Genetically Modified; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification; D013154:Spleen / Q000276:immunology; D014026:Nicotiana; D014611:Vaccination / Q000379:methods*
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D001427:Bacterial Toxins; D036022:Capsid Proteins; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D009856:Oncogene Proteins, Viral; D053918:Papillomavirus Vaccines; D011994:Recombinant Proteins; C063317:L1 protein, Human papillomavirus type 16; D007371:Interferon-gamma; C027538:heat-labile enterotoxin, E coli
keywords: HPV16L1; LT-B; mucosal immunity; systemic immunity; transgenic tobacco plants