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Poor Long-Term Efficacy of Prevnar-13 in Sickle Cell Disease Mice Is Associated with an Inability to Sustain Pneumococcal-Specific Antibody Titers

BACKGROUND: One of the most common causes of morbidity and mortality in children with sickle cell disease (SCD) is infection with the pneumococcal bacterium (Streptococcus pneumoniae). Unfortunately, the polysaccharide-conjugate vaccine appears to be less effective in individuals with SCD when compa...

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Autores principales: Szczepanek, Steven M., Roberts, Sean, Rogers, Kara, Cotte, Christina, Adami, Alexander J., Bracken, Sonali J., Salmon, Sharon, Secor, Eric R., Thrall, Roger S., Andemariam, Biree, Metzger, Dennis W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4766082/
https://www.ncbi.nlm.nih.gov/pubmed/26910228
http://dx.doi.org/10.1371/journal.pone.0149261
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author Szczepanek, Steven M.
Roberts, Sean
Rogers, Kara
Cotte, Christina
Adami, Alexander J.
Bracken, Sonali J.
Salmon, Sharon
Secor, Eric R.
Thrall, Roger S.
Andemariam, Biree
Metzger, Dennis W.
author_facet Szczepanek, Steven M.
Roberts, Sean
Rogers, Kara
Cotte, Christina
Adami, Alexander J.
Bracken, Sonali J.
Salmon, Sharon
Secor, Eric R.
Thrall, Roger S.
Andemariam, Biree
Metzger, Dennis W.
author_sort Szczepanek, Steven M.
collection PubMed
description BACKGROUND: One of the most common causes of morbidity and mortality in children with sickle cell disease (SCD) is infection with the pneumococcal bacterium (Streptococcus pneumoniae). Unfortunately, the polysaccharide-conjugate vaccine appears to be less effective in individuals with SCD when compared to the general population. We sought to better understand the relative efficacy of pneumococcal vaccination in a SCD mouse challenge model. METHODS: Transgenic control and SCD mice were monitored for mortality after intranasal pneumococcal infection or pneumococcal vaccination with Prevnar-13 and type-matched challenge. Anti-pneumococcal antibody titers were measured by ELISA and opsonophagocytosis was measured in vitro. RESULTS: Mortality after pneumococcal infection was similar between control and SCD mice. However, after three intramuscular polysaccharide-conjugate vaccinations, all control mice were protected following high-dose intranasal infection, whereas 60% of SCD mice died. Anti-pneumococcal antibody titers showed initial IgG and IgM responses in both groups, but waning titers were observed in the SCD group, even after boosting. When functionally assayed in vitro, serum from SCD mice 13 weeks after a second booster shot maintained little to no ability to opsonize pneumococci, while serum from control mice sustained a significantly higher capacity opsonization. Thus, it appears that SCD mice do not maintain antibody responses to pneumococcal polysaccharides after Prevnar-13 vaccination, thereby leaving them susceptible to mortality after type-matched infection. CONCLUSION: Our results emphasize the need to better understand the correlates of immune protection in SCD so that pneumococcal vaccines can be improved and mortality reduced in this susceptible population.
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spelling pubmed-47660822016-02-26 Poor Long-Term Efficacy of Prevnar-13 in Sickle Cell Disease Mice Is Associated with an Inability to Sustain Pneumococcal-Specific Antibody Titers Szczepanek, Steven M. Roberts, Sean Rogers, Kara Cotte, Christina Adami, Alexander J. Bracken, Sonali J. Salmon, Sharon Secor, Eric R. Thrall, Roger S. Andemariam, Biree Metzger, Dennis W. PLoS One Research Article BACKGROUND: One of the most common causes of morbidity and mortality in children with sickle cell disease (SCD) is infection with the pneumococcal bacterium (Streptococcus pneumoniae). Unfortunately, the polysaccharide-conjugate vaccine appears to be less effective in individuals with SCD when compared to the general population. We sought to better understand the relative efficacy of pneumococcal vaccination in a SCD mouse challenge model. METHODS: Transgenic control and SCD mice were monitored for mortality after intranasal pneumococcal infection or pneumococcal vaccination with Prevnar-13 and type-matched challenge. Anti-pneumococcal antibody titers were measured by ELISA and opsonophagocytosis was measured in vitro. RESULTS: Mortality after pneumococcal infection was similar between control and SCD mice. However, after three intramuscular polysaccharide-conjugate vaccinations, all control mice were protected following high-dose intranasal infection, whereas 60% of SCD mice died. Anti-pneumococcal antibody titers showed initial IgG and IgM responses in both groups, but waning titers were observed in the SCD group, even after boosting. When functionally assayed in vitro, serum from SCD mice 13 weeks after a second booster shot maintained little to no ability to opsonize pneumococci, while serum from control mice sustained a significantly higher capacity opsonization. Thus, it appears that SCD mice do not maintain antibody responses to pneumococcal polysaccharides after Prevnar-13 vaccination, thereby leaving them susceptible to mortality after type-matched infection. CONCLUSION: Our results emphasize the need to better understand the correlates of immune protection in SCD so that pneumococcal vaccines can be improved and mortality reduced in this susceptible population. Public Library of Science 2016-02-24 /pmc/articles/PMC4766082/ /pubmed/26910228 http://dx.doi.org/10.1371/journal.pone.0149261 Text en © 2016 Szczepanek 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 (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Szczepanek, Steven M.
Roberts, Sean
Rogers, Kara
Cotte, Christina
Adami, Alexander J.
Bracken, Sonali J.
Salmon, Sharon
Secor, Eric R.
Thrall, Roger S.
Andemariam, Biree
Metzger, Dennis W.
Poor Long-Term Efficacy of Prevnar-13 in Sickle Cell Disease Mice Is Associated with an Inability to Sustain Pneumococcal-Specific Antibody Titers
title Poor Long-Term Efficacy of Prevnar-13 in Sickle Cell Disease Mice Is Associated with an Inability to Sustain Pneumococcal-Specific Antibody Titers
title_full Poor Long-Term Efficacy of Prevnar-13 in Sickle Cell Disease Mice Is Associated with an Inability to Sustain Pneumococcal-Specific Antibody Titers
title_fullStr Poor Long-Term Efficacy of Prevnar-13 in Sickle Cell Disease Mice Is Associated with an Inability to Sustain Pneumococcal-Specific Antibody Titers
title_full_unstemmed Poor Long-Term Efficacy of Prevnar-13 in Sickle Cell Disease Mice Is Associated with an Inability to Sustain Pneumococcal-Specific Antibody Titers
title_short Poor Long-Term Efficacy of Prevnar-13 in Sickle Cell Disease Mice Is Associated with an Inability to Sustain Pneumococcal-Specific Antibody Titers
title_sort poor long-term efficacy of prevnar-13 in sickle cell disease mice is associated with an inability to sustain pneumococcal-specific antibody titers
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4766082/
https://www.ncbi.nlm.nih.gov/pubmed/26910228
http://dx.doi.org/10.1371/journal.pone.0149261
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