Humoral immunity in patients with chronic kidney disease and their response to pneumococcal immunization
Doctor of Philosophy
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In northwestern Ontario the Indigenous First Nations (FN) population have an increased prevalence of chronic kidney disease (CKD). There is an increased rate of infectious disease caused by Streptococcus pneumoniae (pneumococcus) and Haemophilus influenzae in the FN population. The 23-valent pneumococcal polysaccharide vaccine (PPV23) and 13-valent pneumococcal protein-polysaccharide conjugate vaccine (PCV13) are used to prevent pneumococcal disease in Canada. Since the implementation of H. influenzae type b (Hib) vaccine programs, invasive H. influenzae type a (Hia) disease has replaced invasive Hib disease in the FN population. However, there is no vaccine to prevent disease caused by non-Hib strains. To maintain immunological memory in adults, stimulation of pre-existing memory is achieved through immunization. To determine if patients with CKD have the ability to respond to conjugate vaccines specific for Hia or pneumococcus, naturally acquired humoral immunity against these pathogens must be evaluated. Immunization with PPV23 is recommended for adults with CKD, however PPV23 is suboptimal at inducing antibody responses in adults with CKD compared to healthy adults. PCV13 is recommended for certain immunocompromised adults, but only two studies evaluated the immunogenicity of PCV13 in adults with CKD with conflicting results. To determine if PCV13 is immunogenic in patients with CKD and the effect of previous PPV23 immunization on subsequent immunization with PCV13, quantification of Bcell subpopulations, pneumococcal specific B cells and their relationship with antibody responses to PCV13 must be evaluated. The results suggest that the increased prevalence of invasive disease caused by pneumococcus and Hia in the FN population is not due to decreased numbers of B cells or concentrations of naturally acquired antibodies. The increased prevalence of diseases such as CKD causing immune dysfunction in a higher proportion of the FN population increases their risk for invasive disease. Results suggest that a new Hia-conjugate vaccine may be immunogenic in adults with CKD, as it will potentially re-activate Hia specific immunological memory. Our findings suggest that previous immunization with PPV23 has a negative effect on the humoral immune response that results in long-term changes in B-cell subpopulations and decreases antibody responses to subsequent immunization with PCV13 in patients with CKD.