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Decreased Response After Conjugated Meningococcal Serogroup C Vaccination in Children With Down Syndrome

Kusters, Maaike A. MD; Jol-Van Der Zijde, Els C. M. BASC; Gijsbers, Rianne H. J. M. MSc; de Vries, Esther MD, PhD

The Pediatric Infectious Disease Journal: September 2011 - Volume 30 - Issue 9 - p 818-819
doi: 10.1097/INF.0b013e31822233f9
Letters to the Editor

Department of Pediatrics, Jeroen Bosch Hospital (Kusters)

Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands (Jol-Van Der Zijde)

Department of Pediatrics, Jeroen Bosch Hospital, ′s-Hertogenbosch, The Netherlands (Gijsbers, de Vries)

The authors have no funding or conflicts of interest to disclose.

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To the Editors:

Meningococcal serogroup C conjugate (MenC) vaccine is a part of the Dutch immunization program since 2002. In the MenC vaccine, the polysaccharide antigen is linked to the protein carrier tetanus toxoid with the aim to achieve an adequate immune response at an early age, which would not be possible with a pure polysaccharide vaccine. The immune response to a conjugate vaccine is characterized by T-cell-dependent isotype switching to IgG-antibodies, especially IgG1, and induction of immunologic memory.

In a catch-up campaign, all children (1–18 years) were offered a single dose of MenC in the Netherlands in 2002. Blood samples were obtained from 19 children (mean age, 10.6; range, 5.3–17.4 years) with Down syndrome (DS) during regular hospital visits 3 months (n = 7; mean, 13 weeks; range, 39–107 days), or around 1 year (n = 12; mean, 50 weeks; range, 275–447 days), after this single dose of MenC vaccination. MenC polysaccharide (PS)-specific IgG, IgM, and IgA concentrations were measured using an antibody capture enzyme-linked immunosorbent assay.1 Results were compared with reference values of healthy adults from the same laboratory, 1 month (n = 12) and 1 year (n = 11) after single MenC vaccination.

At 3 months postvaccination, geometric mean MenC/PS-specific IgG, IgA, and IgM serum values were 5.5 (range, 1.4–41), 0.71 (0.03–11), and 0.61 (0.10–7.5) μg/mL, compared with 26 (5.6–59), 5.6 (2.1–11), and 5.2 (1.7–35) μg/mL in healthy controls (P = 0.014, 0.028, and 0.12 were assessed by Mann-Whitney U test, respectively). One year after vaccination, geometric mean MenC/PS-specific IgG, IgA, and IgM values were 2.7 (0.78–15), 0.19 (0.02–1.2), and 0.28 (0.15–0.76) μg/mL, whereas reference values were 4.5 (0.68–19), 0.79 (0.13–3.8), and 0.71 (0.16–5.1) μg/mL (P = 0.204, 0.019, <0.001 were assessed by Mann-Whitney U test, respectively). The 19 children with DS did reach protective, but lower levels of vaccine protection after a single MenC vaccination, in comparison with healthy adults, despite the fact that 9 of them showed hypergammaglobulinemia according to age-matched reference values.2

Assaying specific antibody production against well-defined antigens can be used as a model to assess T-cell-dependent (antiprotein) and T-cell-independent (antipolysaccharide) antibody responses; conjugated protein-polysaccharide vaccines like MenC show aspects of both the types of responses. Impaired specific antibody responses to unconjugated pneumococcal polysaccharide have been described in DS, suggesting a B-lymphocyte problem.3 Impaired responses to influenza, hepatitis B, and tetanus (protein prototype) have been described as well, suggesting an additional T-lymphocyte or T-B interaction problem.3 Not unexpectedly, therefore, our data show that protein conjugation does not fully overcome the impaired antibody production to this polysaccharide antigen in DS.

Of course, decreased antibody production upon vaccination may have clinical implications as well. Children with DS have frequent respiratory infections, but an increased frequency of meningococcal disease has not been described in recent surveys, either in the pre-4 or post-MenC5 era, but specific attention was not given to this subject. Thus, it is as yet unclear whether children with DS are at greater risk of meningococcal disease, or whether they would benefit from an additional dose of conjugated meningococcal vaccination. Further studies are needed to elucidate this.

Maaike A. Kusters, MD

Department of Pediatrics Jeroen Bosch Hospital

Els C. M. Jol-Van Der Zijde, BASC

Department of Pediatrics Leiden University Medical Center Leiden, The Netherlands

Rianne H. J. M. Gijsbers, MSc

Esther de Vries, MD, PhD

Department of Pediatrics Jeroen Bosch Hospital ′s-Hertogenbosch, The Netherlands

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REFERENCES

1. Gheesling LL, Carlone GM, Pais LB, et al. Multicenter comparison of Neisseria meningitidis serogroup C anti-capsular polysaccharide antibody levels measured by a standardized enzyme-linked immunosorbent assay. J Clin Microbiol. 1994;32:1475–1482.
2. Vlug A, Nieuwenhuys EJ, van Eijk RV, et al. Nephelometric measurements of human IgG subclasses and their reference ranges. Ann Biol Clin (Paris). 1994;52:561–567.
3. Kusters MA, Verstegen RH, Gemen EF, et al. Intrinsic defect of the immune system in children with Down syndrome: a review. Clin Exp Immunol. 2009;156:189–193.
4. Baccichetti C, Lenzini E, Pegoraro R. Down syndrome in the Belluno district (Veneto region, northeast Italy): age distribution and morbidity. Am J Med Genet Suppl. 1990;7:84–86.
5. Day SM, Strauss DJ, Shavelle RM, et al. Mortality and causes of death in persons with Down syndrome in California. Dev Med Child Neurol. 2005;47:171–176.
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