Intranasal immunization with pneumococcal conjugate vaccines with LT-K63, a nontoxic mutant of heat-Labile enterotoxin, as adjuvant rapidly induces protective immunity against lethal pneumococcal infections in neonatal mice

2.50
Hdl Handle:
http://hdl.handle.net/2336/30532
Title:
Intranasal immunization with pneumococcal conjugate vaccines with LT-K63, a nontoxic mutant of heat-Labile enterotoxin, as adjuvant rapidly induces protective immunity against lethal pneumococcal infections in neonatal mice
Authors:
Jakobsen, Håvard; Bjarnarson, Stefania; Del Giudice, Giuseppe; Moreau, Monique; Siegrist, Claire-Anne; Jonsdottir, Ingileif
Citation:
Infect. Immun. 2002, 70(3):1443-52
Issue Date:
1-Mar-2002
Abstract:
Immunization with pneumococcal polysaccharides (PPS) conjugated to tetanus toxoid (TT) (Pnc-TT) elicits protective immunity in an adult murine pneumococcal infection model. To assess immunogenicity and protective immunity in early life, neonatal (1 week old) and infant (3 weeks old) mice were immunized intranasally (i.n.) or subcutaneously (s.c.) with Pnc-TT of serotype 1 (Pnc1-TT). Anti-PPS-1 and anti-TT immunoglobulin G (IgG) and IgM antibodies were measured in serum and saliva, and vaccine-induced protection was evaluated by i.n. challenge with serotype 1 pneumococci. Pnc1-TT was immunogenic in neonatal and infant mice when administered s.c. without adjuvant: a majority of the young mice were protected from bacteremia and a reduction of pneumococcal density in the lungs was observed, although antibody responses and protective efficacy remained lower than in adults. The addition of LT-K63, a nontoxic mutant of heat-labile enterotoxin, as adjuvant significantly enhanced PPS-1-specific IgG responses and protective efficacy following either s.c. or i.n. Pnc1-TT immunization. Mucosal immunization was particularly efficient in neonates, as a single i.n. dose of Pnc1-TT and LT-K63 induced significantly higher PPS-1-specific IgG responses than s.c. immunization and was sufficient to protect neonatal mice against pneumococcal infections, whereas two s.c. doses were required to induce complete protection. In addition, i.n. immunization with Pnc1-TT and LT-K63 induced a vigorous salivary IgA response. This suggests that mucosal immunization with pneumococcal conjugate vaccines and LT-K63 may be able to circumvent some of the limitations of neonatal antibody responses, which are required for protective immunity in early life.
Description:
To access publisher full text version of this article. Please click on the hyperlink in Additional Links field
Additional Links:
http://iai.asm.org/cgi/content/abstract/70/3/1443

Full metadata record

DC FieldValue Language
dc.contributor.authorJakobsen, Håvard-
dc.contributor.authorBjarnarson, Stefania-
dc.contributor.authorDel Giudice, Giuseppe-
dc.contributor.authorMoreau, Monique-
dc.contributor.authorSiegrist, Claire-Anne-
dc.contributor.authorJonsdottir, Ingileif-
dc.date.accessioned2008-06-26T14:07:29Z-
dc.date.available2008-06-26T14:07:29Z-
dc.date.issued2002-03-01-
dc.date.submitted2008-06-26-
dc.identifier.citationInfect. Immun. 2002, 70(3):1443-52en
dc.identifier.issn0019-9567-
dc.identifier.pmid11854231-
dc.identifier.doi10.1128/IAI.70.3.1443-1452.2002-
dc.identifier.urihttp://hdl.handle.net/2336/30532-
dc.descriptionTo access publisher full text version of this article. Please click on the hyperlink in Additional Links fielden
dc.description.abstractImmunization with pneumococcal polysaccharides (PPS) conjugated to tetanus toxoid (TT) (Pnc-TT) elicits protective immunity in an adult murine pneumococcal infection model. To assess immunogenicity and protective immunity in early life, neonatal (1 week old) and infant (3 weeks old) mice were immunized intranasally (i.n.) or subcutaneously (s.c.) with Pnc-TT of serotype 1 (Pnc1-TT). Anti-PPS-1 and anti-TT immunoglobulin G (IgG) and IgM antibodies were measured in serum and saliva, and vaccine-induced protection was evaluated by i.n. challenge with serotype 1 pneumococci. Pnc1-TT was immunogenic in neonatal and infant mice when administered s.c. without adjuvant: a majority of the young mice were protected from bacteremia and a reduction of pneumococcal density in the lungs was observed, although antibody responses and protective efficacy remained lower than in adults. The addition of LT-K63, a nontoxic mutant of heat-labile enterotoxin, as adjuvant significantly enhanced PPS-1-specific IgG responses and protective efficacy following either s.c. or i.n. Pnc1-TT immunization. Mucosal immunization was particularly efficient in neonates, as a single i.n. dose of Pnc1-TT and LT-K63 induced significantly higher PPS-1-specific IgG responses than s.c. immunization and was sufficient to protect neonatal mice against pneumococcal infections, whereas two s.c. doses were required to induce complete protection. In addition, i.n. immunization with Pnc1-TT and LT-K63 induced a vigorous salivary IgA response. This suggests that mucosal immunization with pneumococcal conjugate vaccines and LT-K63 may be able to circumvent some of the limitations of neonatal antibody responses, which are required for protective immunity in early life.en
dc.language.isoenen
dc.publisherAmerican Society For Microbiologyen
dc.relation.urlhttp://iai.asm.org/cgi/content/abstract/70/3/1443en
dc.subject.meshAdjuvants, Immunologicen
dc.subject.meshAdministration, Intranasalen
dc.subject.meshAnimalsen
dc.subject.meshAnimals, Newbornen
dc.subject.meshAntibodies, Bacterialen
dc.subject.meshBacterial Toxinsen
dc.subject.meshEnterotoxinsen
dc.subject.meshEscherichia coli Proteinsen
dc.subject.meshImmunoglobulin Aen
dc.subject.meshMiceen
dc.subject.meshPneumococcal Infectionsen
dc.subject.meshPneumococcal Vaccinesen
dc.subject.meshPolysaccharides, Bacterialen
dc.subject.meshSalivaen
dc.subject.meshVaccinationen
dc.subject.meshVaccines, Conjugateen
dc.titleIntranasal immunization with pneumococcal conjugate vaccines with LT-K63, a nontoxic mutant of heat-Labile enterotoxin, as adjuvant rapidly induces protective immunity against lethal pneumococcal infections in neonatal miceen
dc.typeArticleen
dc.contributor.departmentDepartment of Immunology, Landspitali-University Hospital, Reykjavik, Icelanden
dc.identifier.journalInfection and immunityen
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