title: Oral Delivery of a Novel Recombinant Streptococcus mitis Vector Elicits Robust Vaccine Antigen-Specific Oral Mucosal and Systemic Antibody Responses and T Cell Tolerance.
abstract: The pioneer human oral commensal bacterium Streptococcus mitis has unique biologic features that make it an attractive mucosal vaccine or therapeutic delivery vector. S. mitis is safe as a natural persistent colonizer of the mouth, throat and nasopharynx and the oral commensal bacterium is capable of inducing mucosal antibody responses. A recombinant S. mitis (rS. mitis) that stably expresses HIV envelope protein was generated and tested in the germ-free mouse model to evaluate the potential usefulness of this vector as a mucosal vaccine against HIV. Oral vaccination led to the efficient and persistent bacterial colonization of the mouth and the induction of both salivary and systemic antibody responses. Interestingly, persistently colonized animals developed antigen-specific systemic T cell tolerance. Based on these findings we propose the use of rS. mitis vaccine vector for the induction of mucosal antibodies that will prevent the penetration of the mucosa by pathogens such as HIV. Moreover, the first demonstration of rS. mitis having the ability to elicit T cell tolerance suggest the potential use of rS. mitis as an immunotherapeutic vector to treat inflammatory, allergic and autoimmune diseases.
authors.affiliation: Global Infectious Disease Research Center and the Department of Immunology and Infectious Diseases, The Forsyth Institute, 245 First Street, Cambridge, Massachusetts, United States of America.
authors.forename: Emily
authors.initials: E
authors.lastname: Xie
authors.affiliation: Global Infectious Disease Research Center and the Department of Immunology and Infectious Diseases, The Forsyth Institute, 245 First Street, Cambridge, Massachusetts, United States of America.
authors.forename: Abhiroop
authors.initials: A
authors.lastname: Kotha
authors.affiliation: Global Infectious Disease Research Center and the Department of Immunology and Infectious Diseases, The Forsyth Institute, 245 First Street, Cambridge, Massachusetts, United States of America.
authors.forename: Tracy
authors.initials: T
authors.lastname: Biaco
authors.affiliation: Global Infectious Disease Research Center and the Department of Immunology and Infectious Diseases, The Forsyth Institute, 245 First Street, Cambridge, Massachusetts, United States of America.
authors.forename: Nikita
authors.initials: N
authors.lastname: Sedani
authors.affiliation: Global Infectious Disease Research Center and the Department of Immunology and Infectious Diseases, The Forsyth Institute, 245 First Street, Cambridge, Massachusetts, United States of America.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Zou
authors.affiliation: Global Infectious Disease Research Center and the Department of Immunology and Infectious Diseases, The Forsyth Institute, 245 First Street, Cambridge, Massachusetts, United States of America.|Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, Massachusetts, United States of America.
authors.forename: Phillip
authors.initials: P
authors.lastname: Stashenko
authors.affiliation: Department of Microbiology, The Forsyth Institute, 245 First Street, Cambridge, Massachusetts, United States of America.
authors.forename: Margaret J
authors.initials: MJ
authors.lastname: Duncan
authors.affiliation: Global Infectious Disease Research Center and the Department of Immunology and Infectious Diseases, The Forsyth Institute, 245 First Street, Cambridge, Massachusetts, United States of America.|Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, Massachusetts, United States of America.
authors.forename: Antonio
authors.initials: A
authors.lastname: Campos-Neto
authors.affiliation: Global Infectious Disease Research Center and the Department of Immunology and Infectious Diseases, The Forsyth Institute, 245 First Street, Cambridge, Massachusetts, United States of America.|Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, Massachusetts, United States of America.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Cayabyab
mesh_terms: D016915:AIDS Vaccines / Q000235:genetics / Q000276:immunology*; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D005260:Female; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics*; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000276:immunology; D007108:Immune Tolerance; D051379:Mice; D008807:Mice, Inbred BALB C; D009061:Mouth Mucosa / Q000276:immunology*; D034361:Streptococcus mitis / Q000235:genetics* / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D000914:Antibodies, Viral; D015699:HIV Envelope Protein gp120; D014614:Vaccines, Synthetic