title: Intranasal and sublingual delivery of inactivated polio vaccine.
abstract: Polio is on the brink of eradication. Improved inactivated polio vaccines (IPV) are needed towards complete eradication and for the use in the period thereafter. Vaccination via mucosal surfaces has important potential advantages over intramuscular injection using conventional needle and syringe, the currently used delivery method for IPV. One of them is the ability to induce both serum and mucosal immune responses: the latter may provide protection at the port of virus entry. The current study evaluated the possibilities of polio vaccination via mucosal surfaces using IPV based on attenuated Sabin strains. Mice received three immunizations with trivalent sIPV via intramuscular injection, or via the intranasal or sublingual route. The need of an adjuvant for the mucosal routes was investigated as well, by testing sIPV in combination with the mucosal adjuvant cholera toxin. Both intranasal and sublingual sIPV immunization induced systemic polio-specific serum IgG in mice that were functional as measured by poliovirus neutralization. Intranasal administration of sIPV plus adjuvant induced significant higher systemic poliovirus type 3 neutralizing antibody titers than sIPV delivered via the intramuscular route. Moreover, mucosal sIPV delivery elicited polio-specific IgA titers at different mucosal sites (IgA in saliva, fecal extracts and intestinal tissue) and IgA-producing B-cells in the spleen, where conventional intramuscular vaccination was unable to do so. However, it is likely that a mucosal adjuvant is required for sublingual vaccination. Further research on polio vaccination via sublingual mucosal route should include the search for safe and effective adjuvants, and the development of novel oral dosage forms that improve antigen uptake by oral mucosa, thereby increasing vaccine immunogenicity. This study indicates that both the intranasal and sublingual routes might be valuable approaches for use in routine vaccination or outbreak control in the period after complete OPV cessation and post-polio eradication.
authors.affiliation: Intravacc (Institute for Translational Vaccinology), Bilthoven, The Netherlands. Electronic address: Heleen.kraan@intravacc.nl.
authors.forename: Heleen
authors.initials: H
authors.lastname: Kraan
authors.affiliation: Intravacc (Institute for Translational Vaccinology), Bilthoven, The Netherlands.
authors.forename: Peter
authors.initials: P
authors.lastname: Soema
authors.affiliation: Intravacc (Institute for Translational Vaccinology), Bilthoven, The Netherlands.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Amorij
authors.affiliation: Intravacc (Institute for Translational Vaccinology), Bilthoven, The Netherlands; Division of Drug Delivery Technology, Leiden Academic Center for Drug Research, Leiden University, Leiden, The Netherlands.
authors.forename: Gideon
authors.initials: G
authors.lastname: Kersten
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000281:Administration, Intranasal; D000286:Administration, Sublingual; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000032:analysis / Q000097:blood; D002772:Cholera Toxin / Q000008:administration & dosage; D018928:Immunity, Mucosal; D007115:Immunization Schedule; D007070:Immunoglobulin A / Q000032:analysis; D007074:Immunoglobulin G / Q000097:blood; D007273:Injections, Intramuscular; D008807:Mice, Inbred BALB C; D011054:Poliovirus Vaccine, Inactivated / Q000008:administration & dosage* / Q000276:immunology*; D016896:Treatment Outcome
chemical_list: D000276:Adjuvants, Immunologic; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D011054:Poliovirus Vaccine, Inactivated; D002772:Cholera Toxin
keywords: Adjuvant; Inactivated polio vaccine; Intranasal; Mucosal delivery; Sublingual; Vaccines