title: Poor Long-Term Efficacy of Prevnar-13 in Sickle Cell Disease Mice Is Associated with an Inability to Sustain Pneumococcal-Specific Antibody Titers.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Center of Excellence for Vaccine Research, Department of Pathobiology and Veterinary Science, University of Connecticut, Storrs, CT, United States of America, 06269.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Szczepanek
authors.affiliation: Center for Immunology and Microbial Disease, Albany Medical College, Albany, NY, United States of America, 12208.
authors.forename: Sean
authors.initials: S
authors.lastname: Roberts
authors.affiliation: Center of Excellence for Vaccine Research, Department of Pathobiology and Veterinary Science, University of Connecticut, Storrs, CT, United States of America, 06269.
authors.forename: Kara
authors.initials: K
authors.lastname: Rogers
authors.affiliation: Center of Excellence for Vaccine Research, Department of Pathobiology and Veterinary Science, University of Connecticut, Storrs, CT, United States of America, 06269.
authors.forename: Christina
authors.initials: C
authors.lastname: Cotte
authors.affiliation: Department of Immunology, University of Connecticut Health Center, Farmington, CT, United States of America, 06030.
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Adami
authors.affiliation: Department of Immunology, University of Connecticut Health Center, Farmington, CT, United States of America, 06030.
authors.forename: Sonali J
authors.initials: SJ
authors.lastname: Bracken
authors.affiliation: Center for Immunology and Microbial Disease, Albany Medical College, Albany, NY, United States of America, 12208.
authors.forename: Sharon
authors.initials: S
authors.lastname: Salmon
authors.affiliation: Helen and Harry Gray Cancer Center and Department of Medicine, Division of Integrative Medicine, Hartford Hospital, Hartford, CT, United States of America, 06106.
authors.forename: Eric R
authors.initials: ER
authors.lastname: Secor
authors.affiliation: Department of Immunology, University of Connecticut Health Center, Farmington, CT, United States of America, 06030.
authors.forename: Roger S
authors.initials: RS
authors.lastname: Thrall
authors.affiliation: The Lea's Foundation Center for Hematological Disorders, Neag Comprehensive Cancer Center, University of Connecticut Health Center, Farmington, CT, United States of America, 06030.
authors.forename: Biree
authors.initials: B
authors.lastname: Andemariam
authors.affiliation: Center for Immunology and Microbial Disease, Albany Medical College, Albany, NY, United States of America, 12208.
authors.forename: Dennis W
authors.initials: DW
authors.lastname: Metzger
mesh_terms: D000755:Anemia, Sickle Cell / Q000235:genetics / Q000276:immunology; D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology*; D004195:Disease Models, Animal; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D007075:Immunoglobulin M / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D022242:Pneumococcal Vaccines / Q000276:immunology / Q000494:pharmacology; D013296:Streptococcus pneumoniae / Q000276:immunology*; D013997:Time Factors
chemical_list: C538862:13-valent pneumococcal vaccine; D000907:Antibodies, Bacterial; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D022242:Pneumococcal Vaccines