Influence of the route of immunization and the nature of the bacterial vector on immunogenicity of mucosal vaccines based on lactic acid bacteria.
Mucosal immunity plays a major role in the prevention of infectious diseases. Genetically engineered lactic acid bacteria (LAB) have been tested in the last 10 years as safe mucosal delivery vectors. We previously showed that intranasal co-administration of recombinant lactococci displaying human papillomavirus type 16 (HPV-16) E7 antigen at its surface (LL-E7) and secreting biologically active interleukine-12 (LL-IL-12) has therapeutic effects on HPV-16-induced tumors in mice. In this work, to optimize the immunization protocol, a comparison between intragastric and intranasal routes of administration was performed and two different LAB strains (Lactococcus lactis and Lactobacillus plantarum) were tested as delivery vector. E7-specific systemic and mucosal responses as well as potent anti-tumor effects were higher after intranasal immunization with LL-E7 and LL-IL-12 strains than intragastric administration. Comparisons of the immune responses induced by intranasal administration of either LL-E7 or Lb. plantarum anchoring E7 antigen (LP-E7) revealed highest systemic responses with recombinant Lactobacillus. Furthermore, although only a modest mucosal immune response was observed with LP-E7, this strain was able to induce a significant regression of HPV-induced tumors in contrast to LL-E7. Taken together, our results demonstrate the advantage of intranasal over intragastric route of immunization to induce an antigen-specific immune response and suggest that intrinsic immunomodulatory properties of Lb. plantarum play an important role in the immunogenicity of the expressed antigen.
Unité d'Ecologie et de Physiologie du Système Digestif, INRA, Domaine de Vilvert, 78352 Jouy-en-Josas Cedex, France.
Naima G
NG
Cortes-Perez
François
F
Lefèvre
Gérard
G
Corthier
Karine
K
Adel-Patient
Philippe
P
Langella
Luis G
LG
Bermúdez-Humarán
D000281:Administration, Intranasal; D000818:Animals; D004333:Drug Administration Routes; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005822:Genetic Vectors / Q000235:genetics; D018928:Immunity, Mucosal / Q000276:immunology*; D007114:Immunization / Q000379:methods*; D015151:Immunoblotting; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology; D048191:Lactiplantibacillus plantarum / Q000235:genetics*; D013294:Lactococcus lactis / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D009369:Neoplasms / Q000209:etiology / Q000276:immunology / Q000517:prevention & control; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000276:immunology; D050725:Papillomavirus E7 Proteins; D030361:Papillomavirus Infections / Q000150:complications / Q000276:immunology / Q000517:prevention & control; D053918:Papillomavirus Vaccines / Q000008:administration & dosage / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D053918:Papillomavirus Vaccines; D011993:Recombinant Fusion Proteins; C059731:oncogene protein E7, Human papillomavirus type 16; D018664:Interleukin-12