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Transgenic sickle cell disease mice have high mortality and dysregulated immune responses after vaccination.

Szczepanek SM, Secor ER, Bracken SJ, Guernsey L, Rafti E, Matson A, Thrall RS, Andemariam B - Pediatr. Res. (2013)

Bottom Line: Eight-week-old SCD mice were vaccinated with ovalbumin and aluminum hydroxide weekly for 3 wk by the intraperitoneal or intramuscular route.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.

View Article: PubMed Central - PubMed

Affiliation: Adult Sickle Cell Center, Division of Hematology-Oncology, Lea Center for Hematologic Disorders, University of Connecticut Health Center, Farmington, Connecticut, USA.

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.

Conclusion: 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.

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Related in: MedlinePlus

BAL fluid cytokines measured in response to vaccination. No cytokines were detected above the MDL before vaccination (IL-1β: C57Bl/6 < 0.20 pg/ml, hemizygous = 1.8 pg/ml (SEM, 1.1), SCD = 11 pg/ml (SEM, 4.9); p<0.05) (IL-6: C57Bl/6 < 0.28 pg/ml, hemizygous = 6.5 pg/ml (SEM, 3.5), SCD = 17 pg/l (SEM, 5.9); p<0.05). Bars represent mean levels +/− standard error of the mean. Significant differences were determined by one-way analysis of variance and pairwise comparisons were conducted utilizing the Dunnett’s post-hoc test with SCD serving as the control group. Black bars = C57Bl/6; grey bars = hemizygous; white bars = SCD. *p<0.05
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Figure 4: BAL fluid cytokines measured in response to vaccination. No cytokines were detected above the MDL before vaccination (IL-1β: C57Bl/6 < 0.20 pg/ml, hemizygous = 1.8 pg/ml (SEM, 1.1), SCD = 11 pg/ml (SEM, 4.9); p<0.05) (IL-6: C57Bl/6 < 0.28 pg/ml, hemizygous = 6.5 pg/ml (SEM, 3.5), SCD = 17 pg/l (SEM, 5.9); p<0.05). Bars represent mean levels +/− standard error of the mean. Significant differences were determined by one-way analysis of variance and pairwise comparisons were conducted utilizing the Dunnett’s post-hoc test with SCD serving as the control group. Black bars = C57Bl/6; grey bars = hemizygous; white bars = SCD. *p<0.05

Mentions: In contrast to the hypo-responsiveness exhibited by SCD mice in the production of serum cytokines after vaccination, cytokines in BAL fluid appeared to be higher in SCD mice (Figure 4). BAL fluid IL-1β was not measurable in C57Bl/6 mice post-vaccination (MDL = 0.20 pg/ml) and was significantly higher in SCD mice when compared with either hemizygous mice or C57Bl/6 mice. Similarly, IL-6 was elevated in the BAL fluid of SCD mice when compared with C57Bl/6 mice (not measurable, MDL = 0.28 pg/ml) after vaccination. No differences in post-vaccination BAL fluid IL-6 were observed between hemizygous mice and SCD mice.


Transgenic sickle cell disease mice have high mortality and dysregulated immune responses after vaccination.

Szczepanek SM, Secor ER, Bracken SJ, Guernsey L, Rafti E, Matson A, Thrall RS, Andemariam B - Pediatr. Res. (2013)

BAL fluid cytokines measured in response to vaccination. No cytokines were detected above the MDL before vaccination (IL-1β: C57Bl/6 < 0.20 pg/ml, hemizygous = 1.8 pg/ml (SEM, 1.1), SCD = 11 pg/ml (SEM, 4.9); p<0.05) (IL-6: C57Bl/6 < 0.28 pg/ml, hemizygous = 6.5 pg/ml (SEM, 3.5), SCD = 17 pg/l (SEM, 5.9); p<0.05). Bars represent mean levels +/− standard error of the mean. Significant differences were determined by one-way analysis of variance and pairwise comparisons were conducted utilizing the Dunnett’s post-hoc test with SCD serving as the control group. Black bars = C57Bl/6; grey bars = hemizygous; white bars = SCD. *p<0.05
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Figure 4: BAL fluid cytokines measured in response to vaccination. No cytokines were detected above the MDL before vaccination (IL-1β: C57Bl/6 < 0.20 pg/ml, hemizygous = 1.8 pg/ml (SEM, 1.1), SCD = 11 pg/ml (SEM, 4.9); p<0.05) (IL-6: C57Bl/6 < 0.28 pg/ml, hemizygous = 6.5 pg/ml (SEM, 3.5), SCD = 17 pg/l (SEM, 5.9); p<0.05). Bars represent mean levels +/− standard error of the mean. Significant differences were determined by one-way analysis of variance and pairwise comparisons were conducted utilizing the Dunnett’s post-hoc test with SCD serving as the control group. Black bars = C57Bl/6; grey bars = hemizygous; white bars = SCD. *p<0.05
Mentions: In contrast to the hypo-responsiveness exhibited by SCD mice in the production of serum cytokines after vaccination, cytokines in BAL fluid appeared to be higher in SCD mice (Figure 4). BAL fluid IL-1β was not measurable in C57Bl/6 mice post-vaccination (MDL = 0.20 pg/ml) and was significantly higher in SCD mice when compared with either hemizygous mice or C57Bl/6 mice. Similarly, IL-6 was elevated in the BAL fluid of SCD mice when compared with C57Bl/6 mice (not measurable, MDL = 0.28 pg/ml) after vaccination. No differences in post-vaccination BAL fluid IL-6 were observed between hemizygous mice and SCD mice.

Bottom Line: Eight-week-old SCD mice were vaccinated with ovalbumin and aluminum hydroxide weekly for 3 wk by the intraperitoneal or intramuscular route.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.

View Article: PubMed Central - PubMed

Affiliation: Adult Sickle Cell Center, Division of Hematology-Oncology, Lea Center for Hematologic Disorders, University of Connecticut Health Center, Farmington, Connecticut, USA.

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.

Conclusion: 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.

Show MeSH
Related in: MedlinePlus