Influenza A/H1N1 Vaccination Response Is Inadequate in Down Syndrome Children When the Latest Cut-off Values Are Used

1Dept Pediatrics, Jeroen Bosch Hospital, [Combining Grave Accent]s-Hertogenbosch 2Dept Pediatrics, Màxima Medical Centre, Veldhoven 3Dept Pediatrics, Elkerliek Hospital, Helmond 4Medical Microbiology and Immunology Laboratory, St. Elisabeth Hospital, Tilburg, The Netherlands.
The Pediatric Infectious Disease Journal (Impact Factor: 2.72). 09/2012; 31(12). DOI: 10.1097/INF.0b013e3182737410
Source: PubMed


We determined the response of 48 Down syndrome (DS) children to 2 doses of influenza A/H1N1 vaccination. 92% reached the previously defined protective level (HI titer ≥1:40), but only 27% reached the level of ≥1:110 which was recently described to predict the conventional 50% clinical protection rate in children. Further studies, and potentially adaptations of the schedule, are needed.

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Available from: Elisabeth G Huijskens
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    • "A study has demonstrated that during the outbreak of the pandemic influenza A (H1N1) 2009 virus in Mexico, likelihoods of hospitalization, intubation, and death were respectively 16-fold, 8-fold, and 335-fold greater for DS than non-DS infected individuals [5]. Although anatomic and functional ear–nose–throat abnormalities [6] may favor microbial colonization in DS, the alterations of the immune response [7] [8] [9] [10] [11] [12] [13] [14] play an important role in the development and evolution of infections. It has been suggested that the increased incidence of respiratory "
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    ABSTRACT: Background: Immunodeficiency is an integral aspect of Down syndrome, as demonstrated by the increased susceptibility to infection of affected. Mortality is still higher than in general population, with respiratory infections among the major causes of death. As more people with Down syndrome are living today than ever before, it is indispensable to develop strategies to prevent and cure the associated disorders. Vaccination is the most successful instrument of preventive medicine. Special seasonal influenza and pneumococcal vaccination strategies have been designed for individuals with risk conditions of all ages. Down syndrome individuals are not included in the high-risk categories. Methods: We enrolled in our study 15 children with Down syndrome and their siblings, vaccinated for the first time with seasonal influenza vaccine and receiving a booster dose of a glyco-conjugated pneumococcal vaccine. We compared the immunological features and response to vaccination measuring serum antibody titers and frequency of specific memory B cells. Results: We confirm that a severe reduction of switched memory B cells is always associated to Down syndrome. After primary vaccination Down syndrome children generate significantly less specific switched memory B cells than their siblings. The response to a booster dose of vaccine is instead comparable in both groups. The production of specific antibodies was equally effective in Down syndrome and controls both after primary and secondary immunization. Conclusions: Down syndrome individuals should be considered a high risk group, because of their increased susceptibility to infection and reduced number of switched memory B cells. Tailored vaccination protocols are needed in order to reduce their burden of infections throughout life.
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    ABSTRACT: We investigated the anti-polysaccharide antibody responses in subjects with Down syndrome (DS) because DS subjects show decreased peripheral B-lymphocyte numbers in all age groups, and a clinical picture of recurrent respiratory tract infections and increased incidence of autoimmune diseases which is reminiscent of common variable immunodeficiency disorders (CVID)-like disease. We determined titers and opsonophagocytosis in response to conjugated and unconjugated pneumococcal serotypes in 18 DS subjects aged 6-24 years. The results show adequate serotype-specific antibody titers in response to all conjugated and almost all unconjugated serotypes used. Opsonophagocytosis activity as measured against pneumococcal serotypes 9N, 19F and 23F was also found to be intact. We conclude that DS subjects do not have a clear defect in their anti-polysaccharide antibody response.
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    ABSTRACT: Children with Down syndrome have increased susceptibility to infections and a high frequency of leukemia and autoimmune disorders, suggesting that immunodeficiency and immune dysfunction are integral parts of the syndrome. A reduction in B-cell numbers has been reported, associated with moderate immunodeficiency and normal immunoglobulin levels. Here we compared B-cell populations of 19 children with Down syndrome with those in healthy age-matched controls. We found that all steps of peripheral B-cell development are altered in Down syndrome, with a more severe defect during the later stages of B-cell development. Transitional and mature-naïve B-cell numbers are reduced by 50% whereas switched memory B cells represent 10-15% of the numbers in age-matched controls. Serum IgM levels were slightly reduced, but all other immunoglobulin isotypes were in the normal range. The frequency of switched memory B cells specific for vaccine antigens was significantly lower in affected children than in their equivalently vaccinated siblings. In vitro switched memory B cells of patients with Down syndrome have an increased ability to differentiate into antibody-forming cells in response to TLR9 signals. Tailored vaccination schedules increasing the number of switched memory B cells may improve protection and reduce the risk of death from infection in Down syndrome. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Full-text · Article · Mar 2015 · European Journal of Immunology