title: Serum and mucosal antibody responses to inactivated polio vaccine after sublingual immunization using a thermoresponsive gel delivery system.
abstract: Administering vaccines directly to mucosal surfaces can induce both serum and mucosal immune responses. Mucosal responses may prevent establishment of initial infection at the port of entry and subsequent dissemination to other sites. The sublingual route is attractive for mucosal vaccination, but both a safe, potent adjuvant and a novel formulation are needed to achieve an adequate immune response. We report the use of a thermoresponsive gel (TRG) combined with a double mutant of a bacterial heat-labile toxin (dmLT) for sublingual immunization with a trivalent inactivated poliovirus vaccine (IPV) in mice. This TRG delivery system, which changes from aqueous solution to viscous gel upon contact with the mucosa at body temperature, helps to retain the formulation at the site of delivery and has functional adjuvant activity from the inclusion of dmLT. IPV was administered to mice either sublingually in the TRG delivery system or intramuscularly in phosphate-buffered saline. We measured poliovirus type-specific serum neutralizing antibodies as well as polio-specific serum Ig and IgA antibodies in serum, saliva, and fecal samples using enzyme-linked immunosorbent assays. Mice receiving sublingual vaccination via the TRG delivery system produced both mucosal and serum antibodies, including IgA. Intramuscularly immunized animals produced only serum neutralizing and binding Ig but no detectable IgA. This study provides proof of concept for sublingual immunization using the TRG delivery system, comprising a thermoresponsive gel and dmLT adjuvant.
authors.affiliation: a PATH ; Seattle , WA USA.
authors.forename: Jessica A
authors.initials: JA
authors.lastname: White
authors.forename: Jeremy S
authors.initials: JS
authors.lastname: Blum
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Hosken
authors.forename: Joshua O
authors.initials: JO
authors.lastname: Marshak
authors.forename: Lauren
authors.initials: L
authors.lastname: Duncan
authors.forename: Changcheng
authors.initials: C
authors.lastname: Zhu
authors.forename: Elizabeth B
authors.initials: EB
authors.lastname: Norton
authors.forename: John D
authors.initials: JD
authors.lastname: Clements
authors.forename: David M
authors.initials: DM
authors.lastname: Koelle
authors.forename: Dexiang
authors.initials: D
authors.lastname: Chen
authors.forename: William C
authors.initials: WC
authors.lastname: Weldon
authors.forename: M Steven
authors.initials: MS
authors.lastname: Oberste
authors.forename: Manjari
authors.initials: M
authors.lastname: Lal
mesh_terms: D000286:Administration, Sublingual; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis*; D016503:Drug Delivery Systems; D005260:Female; D005782:Gels; D018928:Immunity, Mucosal; D007114:Immunization; D007070:Immunoglobulin A / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D011054:Poliovirus Vaccine, Inactivated / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D005782:Gels; D007070:Immunoglobulin A; D011054:Poliovirus Vaccine, Inactivated
keywords: CT, cholera toxin; DPBS, Dulbecco's phosphate-buffered saline; DU, D-antigen units; ELISA, enzyme-linked immunosorbent assay; IM, intramuscular; IPV, inactivated poliovirus vaccine; IgA, immunoglobulin A; IgG, immunoglobulin G; OPV, oral poliovirus vaccine; PBS, phosphate-buffered saline; RT, room temperature; SL, sublingual; SSI, Staten Serum Institute; TMB, tetramethylbenzidine; TRG, thermoresponsive gel; adjuvants; dmLT; dmLT, double mutant heat-labile toxin; mucosal immune response; poliovirus; sublingual immunization; thermoresponsive gel; vaccine delivery