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Sustained protection in mice immunized with fractional doses of Salmonella Enteritidis core and O polysaccharide-flagellin glycoconjugates.
- Source :
-
PloS one [PLoS One] 2013 May 31; Vol. 8 (5), pp. e64680. Date of Electronic Publication: 2013 May 31 (Print Publication: 2013). - Publication Year :
- 2013
-
Abstract
- Non-typhoidal Salmonella (NTS) serovars S. Enteritidis and S. Typhimurium are a major cause of invasive bacterial disease (e.g., bacteremia, meningitis) in infants and young children in sub-Saharan Africa and also occasionally cause invasive disease in highly susceptible hosts (young infants, the elderly, and immunocompromised subjects) in industrialized countries. No licensed vaccines exist against human NTS infections. NTS core and O polysaccharide (COPS) and FliC (Phase 1 flagellin subunits) each constitute protective antigens in murine models. S. Enteritidis COPS conjugated to FliC represents a promising vaccine approach that elicits binding and opsonophagocytic antibodies and protects mice against lethal challenge with virulent S. Enteritidis. We examined the protective efficacy of fractional dosages of S. Enteritidis COPS:FliC conjugate vaccines in mice, and also established that protection can be passively transferred to naïve mice by administering sera from mice immunized with conjugate. Mice were immunized with three doses of either 10 µg, 2.5 µg (full dose), 0.25 µg, or 0.025 µg S. Enteritidis COPS:FliC conjugate at 28 day intervals. Antibody titers to COPS and FliC measured by ELISA fell consonant with progressively smaller vaccine dosage levels; anti-FliC IgG responses remained robust at fractional dosages for which anti-COPS serum IgG titers were decreased. Nevertheless, >90% protection against intraperitoneal challenge was observed in mice immunized with fractional dosages of conjugate that elicited diminished titers to both FliC and COPS. Passive transfer of immune sera from mice immunized with the highest dose of COPS:FliC to naïve mice was also protective, demonstrating the role of antibodies in mediating protection. These results provide important insights regarding the potency of Salmonella glycoconjugate vaccines that use flagellin as a carrier protein.
- Subjects :
- Animals
Antibodies, Bacterial blood
Dose-Response Relationship, Immunologic
Female
Flagellin chemistry
Glycoconjugates administration & dosage
Glycoconjugates chemistry
Humans
Immune Sera administration & dosage
Immunoglobulin G blood
Mice
O Antigens chemistry
Salmonella Infections, Animal immunology
Salmonella Infections, Animal microbiology
Salmonella Vaccines administration & dosage
Salmonella enteritidis drug effects
Vaccination
Vaccines, Conjugate
Flagellin immunology
Glycoconjugates immunology
Immunization, Passive
O Antigens immunology
Salmonella Infections, Animal prevention & control
Salmonella Vaccines immunology
Salmonella enteritidis immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 8
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 23741368
- Full Text :
- https://doi.org/10.1371/journal.pone.0064680