title: Transgenic sickle cell disease mice have high mortality and dysregulated immune responses after vaccination.
abstract: BACKGROUND
  Children with sickle cell disease (SCD) are susceptible to recurrent infections, which are often life threatening and necessitate frequent vaccinations. Given the altered baseline immunity and proinflammatory state associated with SCD, we sought to determine the relative safety and efficacy of vaccination in transgenic SCD mice.
  
  
  METHODS
  Eight-week-old SCD mice were vaccinated with ovalbumin and aluminum hydroxide weekly for 3 wk by the intraperitoneal or intramuscular route. One week after the third vaccination, serum cytokines/chemokines, immunoglobulins, and bronchoalveolar lavage fluid cytokines were measured.
  
  
  RESULTS
  Only SCD mice were prone to mortality associated with vaccination, as 40% of the animals died after the intraperitoneal vaccinations and 50% died after the intramuscular vaccinations. Serum IgG2b and IgM were significantly lower in SCD mice than in C57BL/6 mice after vaccination, but ovalbumin-specific IgE was significantly higher. Serum interleukin (IL)-1α, IL-2, IL-5, macrophage inflammatory protein 1α, and granulocyte macrophage-colony stimulating factor were significantly lower in SCD mice than in C57BL/6 mice after vaccination, whereas bronchoalveolar lavage fluid IL-1β and IL-6 were increased.
  
  
  CONCLUSIONS
  Mice with SCD appear to have a dysregulated immune response to vaccination. Thus, the relative safety and immunogenicity of vaccination should be studied in greater detail in the context of SCD.
authors.affiliation: Adult Sickle Cell Center, Division of Hematology-Oncology, Lea Center for Hematologic Disorders, University of Connecticut Health Center, Farmington, Connecticut, USA.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Szczepanek
authors.forename: Eric R
authors.initials: ER
authors.lastname: Secor
authors.forename: Sonali J
authors.initials: SJ
authors.lastname: Bracken
authors.forename: Linda
authors.initials: L
authors.lastname: Guernsey
authors.forename: Ektor
authors.initials: E
authors.lastname: Rafti
authors.forename: Adam
authors.initials: A
authors.lastname: Matson
authors.forename: Roger S
authors.initials: RS
authors.lastname: Thrall
authors.forename: Biree
authors.initials: B
authors.lastname: Andemariam
mesh_terms: D000536:Aluminum Hydroxide / Q000008:administration & dosage / Q000009:adverse effects; D000704:Analysis of Variance; D000755:Anemia, Sickle Cell / Q000276:immunology*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D016207:Cytokines / Q000097:blood / Q000276:immunology; D005260:Female; D007136:Immunoglobulins / Q000097:blood / Q000276:immunology; D007273:Injections, Intramuscular; D051379:Mice; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000008:administration & dosage / Q000009:adverse effects; D014611:Vaccination / Q000009:adverse effects* / Q000401:mortality*
chemical_list: D016207:Cytokines; D007136:Immunoglobulins; D000536:Aluminum Hydroxide; D010047:Ovalbumin