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Title: Humoral immune responses to pneumococcal disease and vaccination
Author: Stanford, Elaine Yvonne
ISNI:       0000 0004 2746 0752
Awarding Body: Manchester Metropolitan University
Current Institution: Manchester Metropolitan University
Date of Award: 2012
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Background: Streptococcus pneumoniae causes infections in children, older adults and the immunocompromised. This thesis investigates humoral immune responses to pneumococcal vaccination in asplenic adults, and responses to infection and vaccination in children with invasive pneumococcal disease (IPD). Methods: Pneumococal serotype-specific antibody was measured using IgG enzyme-linked immunosorbent assay (asplenic adults), multiplexed bead assays (lgG and IgA) and opsonophagocytic assay (children with IPD), and total IgG was measured using nephelometry. Results: Seven-valent pneumococcal conjugate vaccine (PCV7) elicited significant increases (p <0.01) in vaccine-serotype specific IgG from levels pre-to 3-6 weeks post-vaccination in III asplenic adults. Although 97% (108/111) previously had ~ 1 dose(s) of pneumococcal polysaccharide vaccine, compliance with other UK guidelines for prevention of post-splenectomy infection (meningococcal vaccines and antibiotic prophylaxis) was poor. PCV7 in children with IPD was immunogenic for vaccine serotypes, with IgG GMCs higher in the group immunised under the original licensed schedule than those under a reduced schedule for serotypes 4, 14, 19F and 23F (p <0.05). Thirteen children with age-appropriate vaccination, however, failed to respond to their infecting serotype following additional PCV7 vaccination; this immunological unresponsiveness persisted despite up to 2 further doses. This was the first reported observation of this phenomenon, which has since been seen in association with asymptomatic carriage of vaccine-serotype pneumococci. Conclusion: Although PCV7 was immunogenic in children with IPD and adults with asplenia, protection should not be assumed for individuals colonised by, or infected with, a vaccine serotype when vaccinated. Further work is required to investigate causes of immunological unresponsiveness.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available