title: Oral immunization with a Lactobacillus casei vaccine expressing human papillomavirus (HPV) type 16 E7 is an effective strategy to induce mucosal cytotoxic lymphocytes against HPV16 E7.
abstract: Although many clinical trials on human papillomavirus (HPV) therapeutic vaccines have been performed, clinical responses have not been consistent. We have addressed mucosal cytotoxic cellular immune responses to HPV16 E7 after oral immunization of mice with recombinant Lactobacillus casei expressing HPV16 E7 (LacE7). C57BL/6 mice were orally exposed to 0.1-100mg/head of attenuated LacE7 or vehicle (Lac) vaccines at weeks 1, 2, 4, and 8. Responses to subcutaneous or intramuscular injection of an HPV16 E7 fusion protein using the same timing protocol were used for comparison. Oral immunization with LacE7 elicited E7-specific IFN gamma-producing cells (T cells with E7-type 1 immune responses) among integrin alpha 4 beta 7(+) mucosal lymphocytes collected from gut mucosa. An induction of E7-specific granzyme B-producing cells (E7-CTL) exhibiting killer responses toward HPV16 E7-positive cells was also observed. The induction of T cells with specific mucosal E7-type 1 immune responses was greater after oral immunization with LacE7 when compared to subcutaneous or intramuscular antigen delivery. Oral immunization with Lactobacillus-based vaccines was also able to induce mucosal cytotoxic cellular immune responses. This novel approach at a therapeutic HPV vaccine may achieve more effective clinical responses through its induction of mucosal E7-specific CTL.
authors.affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Adachi
authors.forename: Kei
authors.initials: K
authors.lastname: Kawana
authors.forename: Terufumi
authors.initials: T
authors.lastname: Yokoyama
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Fujii
authors.forename: Ayako
authors.initials: A
authors.lastname: Tomio
authors.forename: Shiho
authors.initials: S
authors.lastname: Miura
authors.forename: Kensuke
authors.initials: K
authors.lastname: Tomio
authors.forename: Satoko
authors.initials: S
authors.lastname: Kojima
authors.forename: Katsutoshi
authors.initials: K
authors.lastname: Oda
authors.forename: Tomomitsu
authors.initials: T
authors.lastname: Sewaki
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Yasugi
authors.forename: Shiro
authors.initials: S
authors.lastname: Kozuma
authors.forename: Yuji
authors.initials: Y
authors.lastname: Taketani
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D005260:Female; D005822:Genetic Vectors; D018928:Immunity, Mucosal; D007273:Injections, Intramuscular; D007279:Injections, Subcutaneous; D007371:Interferon-gamma / Q000096:biosynthesis; D007780:Lacticaseibacillus casei / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D050725:Papillomavirus E7 Proteins / Q000235:genetics / Q000276:immunology*; D053918:Papillomavirus Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014611:Vaccination / Q000379:methods*
chemical_list: D001428:Bacterial Vaccines; D050725:Papillomavirus E7 Proteins; D053918:Papillomavirus Vaccines; C059731:oncogene protein E7, Human papillomavirus type 16; D007371:Interferon-gamma