Sustained Protection in Mice Immunized with Fractional Doses of Salmonella Enteritidis Core and O Polysaccharide-Flagellin Glycoconjugates

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 el...

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Autores principales: Simon, Raphael, Wang, Jin Y., Boyd, Mary A., Tulapurkar, Mohan E., Ramachandran, Girish, Tennant, Sharon M., Pasetti, Marcela, Galen, James E., Levine, Myron M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3669428/
https://www.ncbi.nlm.nih.gov/pubmed/23741368
http://dx.doi.org/10.1371/journal.pone.0064680
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author Simon, Raphael
Wang, Jin Y.
Boyd, Mary A.
Tulapurkar, Mohan E.
Ramachandran, Girish
Tennant, Sharon M.
Pasetti, Marcela
Galen, James E.
Levine, Myron M.
author_facet Simon, Raphael
Wang, Jin Y.
Boyd, Mary A.
Tulapurkar, Mohan E.
Ramachandran, Girish
Tennant, Sharon M.
Pasetti, Marcela
Galen, James E.
Levine, Myron M.
author_sort Simon, Raphael
collection PubMed
description 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.
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spelling pubmed-36694282013-06-05 Sustained Protection in Mice Immunized with Fractional Doses of Salmonella Enteritidis Core and O Polysaccharide-Flagellin Glycoconjugates Simon, Raphael Wang, Jin Y. Boyd, Mary A. Tulapurkar, Mohan E. Ramachandran, Girish Tennant, Sharon M. Pasetti, Marcela Galen, James E. Levine, Myron M. PLoS One Research Article 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. Public Library of Science 2013-05-31 /pmc/articles/PMC3669428/ /pubmed/23741368 http://dx.doi.org/10.1371/journal.pone.0064680 Text en © 2013 Simon et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Simon, Raphael
Wang, Jin Y.
Boyd, Mary A.
Tulapurkar, Mohan E.
Ramachandran, Girish
Tennant, Sharon M.
Pasetti, Marcela
Galen, James E.
Levine, Myron M.
Sustained Protection in Mice Immunized with Fractional Doses of Salmonella Enteritidis Core and O Polysaccharide-Flagellin Glycoconjugates
title Sustained Protection in Mice Immunized with Fractional Doses of Salmonella Enteritidis Core and O Polysaccharide-Flagellin Glycoconjugates
title_full Sustained Protection in Mice Immunized with Fractional Doses of Salmonella Enteritidis Core and O Polysaccharide-Flagellin Glycoconjugates
title_fullStr Sustained Protection in Mice Immunized with Fractional Doses of Salmonella Enteritidis Core and O Polysaccharide-Flagellin Glycoconjugates
title_full_unstemmed Sustained Protection in Mice Immunized with Fractional Doses of Salmonella Enteritidis Core and O Polysaccharide-Flagellin Glycoconjugates
title_short Sustained Protection in Mice Immunized with Fractional Doses of Salmonella Enteritidis Core and O Polysaccharide-Flagellin Glycoconjugates
title_sort sustained protection in mice immunized with fractional doses of salmonella enteritidis core and o polysaccharide-flagellin glycoconjugates
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3669428/
https://www.ncbi.nlm.nih.gov/pubmed/23741368
http://dx.doi.org/10.1371/journal.pone.0064680
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