Haemophilus influenzae type b vaccine failure in children is associated with inadequate production of high-quality antibody.
BACKGROUND: Despite the excellent immunogenicity of Haemophilus influenzae type b (Hib) conjugate vaccines, breakthrough cases of Hib disease still affect a small proportion of vaccinated children in the United Kingdom. We performed a retrospective study to compare the avidity of antibody directed...
| Autores principales: | , , , , , , , , |
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| Formato: | Journal article |
| Lenguaje: | English |
| Publicado: |
2008
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| _version_ | 1826280440290344960 |
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| author | Lee, Y Kelly, D Yu, L Slack, M Booy, R Heath, P Siegrist, C Moxon, R Pollard, A |
| author_facet | Lee, Y Kelly, D Yu, L Slack, M Booy, R Heath, P Siegrist, C Moxon, R Pollard, A |
| author_sort | Lee, Y |
| collection | OXFORD |
| description | BACKGROUND: Despite the excellent immunogenicity of Haemophilus influenzae type b (Hib) conjugate vaccines, breakthrough cases of Hib disease still affect a small proportion of vaccinated children in the United Kingdom. We performed a retrospective study to compare the avidity of antibody directed against the Hib polysaccharide capsule (PRP) in children who experienced Hib vaccine failure in the United Kingdom among 3 historical cohorts and with age-matched healthy control subjects. METHODS: Serum samples from vaccinated children with invasive Hib disease were collected beginning in 1992 as part of enhanced surveillance for Hib disease following vaccine introduction. A total of 251 children who experienced Hib vaccine failure were identified from 3 historical cohorts (1992-1995, 1996-1999, and 2000-2003). The anti-PRP antibody concentration and avidity from healthy age-matched control subjects was obtained for the 3 contemporary time points (1995, 1999, and 2002). Serum anti-PRP antibody concentration was measured in each of the samples using a standard Hib ELISA, and antibody avidity was determined using thiocyanate elution. RESULTS: Within the first 60 days after disease onset, there was no change in the anti-PRP antibody avidity, and there was no statistically significant difference in the geometric mean Hib antibody avidity over the 3 study periods. However, the children who experienced Hib vaccine failure had significantly lower Hib antibody avidity than did healthy control subjects, despite a marked antibody response following infection. CONCLUSIONS: Children who experience Hib disease despite vaccination appear to have a defect in immunological priming, leading to a qualitative difference in Hib-specific memory B cells. Low anti-PRP antibody avidity decreases the functional activity of anti-PRP antibody in the sera of these children experiencing vaccine failure, leading to disease susceptibility. |
| first_indexed | 2024-03-07T00:13:45Z |
| format | Journal article |
| id | oxford-uuid:7a238db6-202b-4be7-95ba-76f732c1cdd1 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T00:13:45Z |
| publishDate | 2008 |
| record_format | dspace |
| spelling | oxford-uuid:7a238db6-202b-4be7-95ba-76f732c1cdd12022-03-26T20:41:53ZHaemophilus influenzae type b vaccine failure in children is associated with inadequate production of high-quality antibody.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:7a238db6-202b-4be7-95ba-76f732c1cdd1EnglishSymplectic Elements at Oxford2008Lee, YKelly, DYu, LSlack, MBooy, RHeath, PSiegrist, CMoxon, RPollard, A BACKGROUND: Despite the excellent immunogenicity of Haemophilus influenzae type b (Hib) conjugate vaccines, breakthrough cases of Hib disease still affect a small proportion of vaccinated children in the United Kingdom. We performed a retrospective study to compare the avidity of antibody directed against the Hib polysaccharide capsule (PRP) in children who experienced Hib vaccine failure in the United Kingdom among 3 historical cohorts and with age-matched healthy control subjects. METHODS: Serum samples from vaccinated children with invasive Hib disease were collected beginning in 1992 as part of enhanced surveillance for Hib disease following vaccine introduction. A total of 251 children who experienced Hib vaccine failure were identified from 3 historical cohorts (1992-1995, 1996-1999, and 2000-2003). The anti-PRP antibody concentration and avidity from healthy age-matched control subjects was obtained for the 3 contemporary time points (1995, 1999, and 2002). Serum anti-PRP antibody concentration was measured in each of the samples using a standard Hib ELISA, and antibody avidity was determined using thiocyanate elution. RESULTS: Within the first 60 days after disease onset, there was no change in the anti-PRP antibody avidity, and there was no statistically significant difference in the geometric mean Hib antibody avidity over the 3 study periods. However, the children who experienced Hib vaccine failure had significantly lower Hib antibody avidity than did healthy control subjects, despite a marked antibody response following infection. CONCLUSIONS: Children who experience Hib disease despite vaccination appear to have a defect in immunological priming, leading to a qualitative difference in Hib-specific memory B cells. Low anti-PRP antibody avidity decreases the functional activity of anti-PRP antibody in the sera of these children experiencing vaccine failure, leading to disease susceptibility. |
| spellingShingle | Lee, Y Kelly, D Yu, L Slack, M Booy, R Heath, P Siegrist, C Moxon, R Pollard, A Haemophilus influenzae type b vaccine failure in children is associated with inadequate production of high-quality antibody. |
| title | Haemophilus influenzae type b vaccine failure in children is associated with inadequate production of high-quality antibody. |
| title_full | Haemophilus influenzae type b vaccine failure in children is associated with inadequate production of high-quality antibody. |
| title_fullStr | Haemophilus influenzae type b vaccine failure in children is associated with inadequate production of high-quality antibody. |
| title_full_unstemmed | Haemophilus influenzae type b vaccine failure in children is associated with inadequate production of high-quality antibody. |
| title_short | Haemophilus influenzae type b vaccine failure in children is associated with inadequate production of high-quality antibody. |
| title_sort | haemophilus influenzae type b vaccine failure in children is associated with inadequate production of high quality antibody |
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