Intranasal immunization with pneumococcal polysaccharide conjugate vaccines with nontoxic mutants of Escherichia coli heat-labile enterotoxins as adjuvants protects mice against invasive pneumococcal infections

2.50
Hdl Handle:
http://hdl.handle.net/2336/47039
Title:
Intranasal immunization with pneumococcal polysaccharide conjugate vaccines with nontoxic mutants of Escherichia coli heat-labile enterotoxins as adjuvants protects mice against invasive pneumococcal infections
Authors:
Jakobsen, H; Schulz, D; Pizza, M; Rappuoli, R; Jonsdottir, I
Citation:
Infect. Immun. 1999, 67(11):5892-7
Issue Date:
1-Nov-1999
Abstract:
Host defenses against Streptococcus pneumoniae depend largely on phagocytosis following opsonization by polysaccharide-specific immunoglobulin G (IgG) antibodies and complement. Since colonization of the respiratory mucosa is the first step in pneumococcal pathogenesis, mucosal immune responses may play a significant role. In addition to inducing systemic immune responses, mucosal vaccination with an effective adjuvant has the advantage of inducing mucosal IgA antibodies. The heat-labile enterotoxin (LT) of Escherichia coli is a well-studied mucosal adjuvant, and adjuvant activity of nontoxic LT mutants has been demonstrated for several protein antigens. We investigated the immunogenicity of pneumococcal polysaccharide conjugate vaccines (PNC) of serotypes 1 and 3 in mice after intranasal (i.n.) immunization by using as an adjuvant the nontoxic LT mutant LT-K63 or LT-R72, which has minimal residual toxicity. Pneumococcal serotype-specific antibodies were measured in serum (IgM, IgG, and IgA) and saliva (IgA), and vaccine-induced protection was evaluated by i.n. challenge with virulent pneumococci of the homologous serotype. When administered with LT mutants, i.n. immunization with both conjugates induced systemic and mucosal immune responses, and serum IgG antibody levels were significantly higher than after subcutaneous immunization. All mice immunized i.n. with PNC-1 and LT mutants were protected against bacteremia and cleared the pneumococci from the lung 24 h after i.n. challenge; pneumococcal density correlated significantly with serum IgG antibody levels. Similarly, the survival of mice immunized i.n. with PNC-3 and LT mutants was significantly prolonged. These results demonstrate that i.n. vaccination with PNC and potent adjuvants can protect mice against invasive and lethal pneumococcal infections, indicating that mucosal vaccination with PNC may be an alternative vaccination strategy for humans.
Description:
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Additional Links:
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Full metadata record

DC FieldValue Language
dc.contributor.authorJakobsen, H-
dc.contributor.authorSchulz, D-
dc.contributor.authorPizza, M-
dc.contributor.authorRappuoli, R-
dc.contributor.authorJonsdottir, I-
dc.date.accessioned2009-01-05T13:22:53Z-
dc.date.available2009-01-05T13:22:53Z-
dc.date.issued1999-11-01-
dc.date.submitted2009-01-05-
dc.identifier.citationInfect. Immun. 1999, 67(11):5892-7en
dc.identifier.issn0019-9567-
dc.identifier.pmid10531245-
dc.identifier.urihttp://hdl.handle.net/2336/47039-
dc.descriptionTo access publisher full text version of this article. Please click on the hyperlink in Additional Links fielden
dc.description.abstractHost defenses against Streptococcus pneumoniae depend largely on phagocytosis following opsonization by polysaccharide-specific immunoglobulin G (IgG) antibodies and complement. Since colonization of the respiratory mucosa is the first step in pneumococcal pathogenesis, mucosal immune responses may play a significant role. In addition to inducing systemic immune responses, mucosal vaccination with an effective adjuvant has the advantage of inducing mucosal IgA antibodies. The heat-labile enterotoxin (LT) of Escherichia coli is a well-studied mucosal adjuvant, and adjuvant activity of nontoxic LT mutants has been demonstrated for several protein antigens. We investigated the immunogenicity of pneumococcal polysaccharide conjugate vaccines (PNC) of serotypes 1 and 3 in mice after intranasal (i.n.) immunization by using as an adjuvant the nontoxic LT mutant LT-K63 or LT-R72, which has minimal residual toxicity. Pneumococcal serotype-specific antibodies were measured in serum (IgM, IgG, and IgA) and saliva (IgA), and vaccine-induced protection was evaluated by i.n. challenge with virulent pneumococci of the homologous serotype. When administered with LT mutants, i.n. immunization with both conjugates induced systemic and mucosal immune responses, and serum IgG antibody levels were significantly higher than after subcutaneous immunization. All mice immunized i.n. with PNC-1 and LT mutants were protected against bacteremia and cleared the pneumococci from the lung 24 h after i.n. challenge; pneumococcal density correlated significantly with serum IgG antibody levels. Similarly, the survival of mice immunized i.n. with PNC-3 and LT mutants was significantly prolonged. These results demonstrate that i.n. vaccination with PNC and potent adjuvants can protect mice against invasive and lethal pneumococcal infections, indicating that mucosal vaccination with PNC may be an alternative vaccination strategy for humans.en
dc.language.isoenen
dc.publisherAmerican Society For Microbiologyen
dc.relation.urlhttp://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=96971en
dc.subject.meshAdjuvants, Immunologicen
dc.subject.meshAdministration, Intranasalen
dc.subject.meshAnimalsen
dc.subject.meshAntibodies, Bacterialen
dc.subject.meshBacterial Toxinsen
dc.subject.meshBacterial Vaccinesen
dc.subject.meshEnterotoxinsen
dc.subject.meshEscherichia colien
dc.subject.meshEscherichia coli Proteinsen
dc.subject.meshFemaleen
dc.subject.meshImmunizationen
dc.subject.meshImmunoglobulin A, Secretoryen
dc.subject.meshMiceen
dc.subject.meshPneumococcal Infectionsen
dc.subject.meshPneumococcal Vaccinesen
dc.subject.meshSerotypingen
dc.subject.meshStreptococcus pneumoniaeen
dc.titleIntranasal immunization with pneumococcal polysaccharide conjugate vaccines with nontoxic mutants of Escherichia coli heat-labile enterotoxins as adjuvants protects mice against invasive pneumococcal infectionsen
dc.typeArticleen
dc.identifier.eissn1098-5522-
dc.contributor.departmentNational University Hospital, Department of Immunology, 101 Reykjavík, Iceland.en
dc.identifier.journalInfection and immunityen
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