title: A single sublingual dose of an adenovirus-based vaccine protects against lethal Ebola challenge in mice and guinea pigs.
abstract: Sublingual (SL) delivery, a noninvasive immunization method that bypasses the intestinal tract for direct entry into the circulation, was evaluated with an adenovirus (Ad5)-based vaccine for Ebola. Mice and guinea pigs were immunized via the intramuscular (IM), nasal (IN), oral (PO) and SL routes. SL immunization elicited strong transgene expression in and attracted CD11c(+) antigen presenting cells to the mucosa. A SL dose of 1 × 10⁸ infectious particles induced Ebola Zaire glycoprotein (ZGP)-specific IFN-γ⁺ T cells in spleen, bronchoalveolar lavage, mesenteric lymph nodes and submandibular lymph nodes (SMLN) of naive mice in a manner similar to the same dose given IN. Ex vivo CFSE and in vivo cytotoxic T lymphocyte (CTL) assays confirmed that SL immunization elicits a notable population of effector memory CD8+ T cells and strong CTL responses in spleen and SMLN. SL immunization induced significant ZGP-specific Th1 and Th2 type responses unaffected by pre-existing immunity (PEI) that protected mice and guinea pigs from lethal challenge. SL delivery protected more mice with PEI to Ad5 than IM injection. SL immunization also reduced systemic anti-Ad5 T and B cell responses in naive mice and those with PEI, suggesting that secondary immunizations could be highly effective for both populations.
authors.affiliation: Division of Pharmaceutics, College of Pharmacy, The University of Texas at Austin, Austin, Texas 78712, United States.
authors.forename: Jin Huk
authors.initials: JH
authors.lastname: Choi
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Schafer
authors.forename: Lihong
authors.initials: L
authors.lastname: Zhang
authors.forename: Gary P
authors.initials: GP
authors.lastname: Kobinger
authors.forename: Terry
authors.initials: T
authors.lastname: Juelich
authors.forename: Alexander N
authors.initials: AN
authors.lastname: Freiberg
authors.forename: Maria A
authors.initials: MA
authors.lastname: Croyle
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000286:Administration, Sublingual; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D000956:Antigens, Viral / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D039521:CD11c Antigen / Q000378:metabolism; D002460:Cell Line; D046129:Ebola Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D029043:Ebolavirus; D006168:Guinea Pigs; D019142:Hemorrhagic Fever, Ebola / Q000276:immunology / Q000401:mortality / Q000517:prevention & control*; D006801:Humans; D007111:Immunity, Cellular; D007117:Immunization, Secondary; D007156:Immunologic Memory; D008297:Male; D051379:Mice; D009061:Mouth Mucosa / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000821:virology; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use; D016019:Survival Analysis; D019076:Transgenes
chemical_list: D000956:Antigens, Viral; D039521:CD11c Antigen; D046129:Ebola Vaccines; D011994:Recombinant Proteins