Transgenic Sickle Cell Disease Mice Have High Mortality and Dysregulated Immune Responses After Vaccination
Medicine and Health Sciences
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.
Eight week-old SCD mice were vaccinated with ovalbumin (OVA) and aluminum hydroxide weekly for three weeks by the intraperitoneal (IP) or intramuscular (IM) route. One week after the third vaccination, serum cytokines/chemokines, immunoglobulins, and bronchoalveolar lavage (BAL) fluid cytokines were measured.
Only SCD mice were prone to mortality associated with vaccination as 40% of the animals died after the IP vaccinations and 50% died after the IM vaccinations. Serum IgG2b and IgM were significantly lower in SCD than C57Bl/6 mice after vaccination, but OVA-specific IgE was significantly higher. Serum interleukin 1 alpha (IL-1α), IL-2, IL-5, macrophage inflammatory protein 1 alpha (MIP-1α), and granulocyte macrophage-colony stimulating factor (GM-CSF) were significantly lower in SCD mice than C57Bl/6 mice after vaccination, whereas BAL fluid IL-1β and IL-6 were elevated.
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.
Szczepanek, Steven M.; Secor, Eric R. Jr; Bracken, Sonali J.; Guernsey, Linda; Rafti, Ektor; Matson, Adam; and Thrall, Roger S., "Transgenic Sickle Cell Disease Mice Have High Mortality and Dysregulated Immune Responses After Vaccination" (2013). UCHC Articles - Research. 280.
Pediatr Res. Author manuscript; available in PMC 2015 Jul 1. Published in final edited form as: Pediatr Res. 2013 Aug; 74(2): 141–147. Published online 2013 May 31. doi: 10.1038/pr.2013.85 PMCID: PMC4487511 NIHMSID: NIHMS560354