B and T cell phenotype and function in children with perinatally acquired HIV-1 infection
Author(s)
Bamford, Alasdair
Type
Thesis
Abstract
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.
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.
Date Issued
2012
Date Awarded
2013-03
Copyright Statement
Attribution NoDerivatives 4.0 International Licence (CC BY-ND)
Advisor
Kelleher, William
Kampmann, Beate
Goldblatt, David
Sponsor
National Institute for Health Research (Great Britain) ; European Society for Paediatric Infectious Diseases
Publisher Department
Medicine
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)