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Title: B and T cell phenotype and function in children with perinatally acquired HIV-1 infection
Author: Bamford, Alasdair
ISNI:       0000 0004 2736 8470
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2013
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Untreated HIV infection is well known to have profound effects on CD4 T cell phenotype and function, ultimately leading to CD4 T cell depletion, AIDS and death. HIV is also known to affect B cell function and phenotype, resulting in impaired and dysregulated humoral immunity. Studies in HIV infected adults have demonstrated that Highly Active Antiretroviral Therapy (HAART) only partially restores B cell phenotype and function. HIV infected adults and children on HAART remain at persistently high risk of pneumococcal disease and mount suboptimal responses to pneumococcal vaccines. The nature of persistent indirect effects of HIV infection on B cell immunity remain under investigated in the paediatric population. Using flow cytometry we have shown that children and adolescents with perinatally acquired (paHIV) have persistent abnormalities in B and T cell phenotype despite fully suppressive HAART. Pneumococcal serotype specific IgG, acquired through natural exposure, was present at baseline, although at a lower concentration than in healthy controls for some serotypes. Vaccination with 13-valent pneumococcal conjugate vaccine (PCV13) was immunogenic, however serological responses to certain serotypes were impaired in comparison to healthy controls. In vitro whole blood cytokine responses to vaccine carrier protein were present at baseline and increased following immunisation, although the diversity and magnitude of antigen specific cytokine release was restricted in comparison to healthy controls. A greater proportion of life spent with undetectable viral load was associated with a more intact B cell phenotype and more robust serotype specific IgG vaccine responses for some vaccine serotypes. Nasopharyngeal pneumococcal carriage isolates were detected in a small proportion of children with paHIV, all of which were non-PCV13 serotypes. These results, while providing an insight into the immunogenicity and mechanism of action of conjugate vaccines outside of the infant period, have wider implications for pneumococcal vaccination and HAART treatment practices for children and adolescents with paHIV.
Supervisor: Kelleher, William ; Kampmann, Beate ; Goldblatt, David Sponsor: National Institute for Health Research ; European Society for Paediatric Infectious Diseases
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral