Spoulou, Vana; (1998) Qualitative and quantitative aspects of immune responses to polysaccharide vaccines in children with HIV infection. Doctoral thesis (M.D.), University College London.

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Abstract

The susceptibility of HIV infected children to bacterial infections, mainly from bacteria with polysaccharide capsule, remains poorly understood. Impaired antibody responses as well as factors related to appropriate isotype production and antibody avidity may be responsible for their vulnerability to infection. Although vaccination with the currently available polysaccharide vaccines is recommended, there is a paucity of data for its real benefits in HIV infected children. The studies presented in this thesis, investigate the quantitative and qualitative aspects of immune responses to polysaccharide vaccines in HIV infected children by measuring levels, isotypes and avidity of antibodies produced after the administration of 23-valent pneumococcal vaccine and Hib-tetanus conjugated vaccine. Since there is a paucity of data to determine long term immunogenicity of the above vaccines, the study population was followed up for a year and persistence of antibodies was monitored in sequential samples taken at 6 and 12 months post vaccination. For that purpose, solid phase assays were developed for the measurement of pneumococcal antibodies to pneumococcal serotypes (PS) 3, 6B, 19F and 23F and cell wall polysaccharide (cps). Immunizations against Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae had similar adverse reaction rates in HIV infected children and controls. Immunogenicity of the 23-valent pneumococcal vaccine and the pattern of IgG2 subclass immune responses, were found similar in seropositive children and controls. Furthermore anti pneumococcal antibody levels were similar at 12 months post vaccination in Human Immunodeficiency Virus (HIV) infected and controls. 84% of HIV infected children achieved protective antibody levels against Hib post immunization, however the mean response was 7.6 fold lower than in controls. In addition, 1 year later only 57% of the initial seropositve responders had persisting titers above the level associated with long term protection (>1 g/ml). For both vaccines there was a significant trend toward poorer responses in children with advanced disease but no correlation with age adjusted CD4 counts. A relation between avidity for PS19F and 23F, and age and stage of the disease could not be established. However, there was some increase in avidity with time, indicated by the higher avidity indices in the 12 months post vaccination samples. This difference was more prominent, when avidity was measured in serum where antibodies against cell wall polysaccharide antibodies (cps) had not been removed. Removal of cps antibodies, resulted in a reduction of avidity indices in most of the samples tested, indicating that cps are high avidity antibodies. The data presented in this thesis, support the policy of vaccinating HIV infected children with polysaccharide vaccines soon after the establishment of diagnosis.

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