Streptococcus pneumoniae is a major cause of morbidity and mortality in HIV infected individuals. Mortality rates remain high despite modern antibiotics, therefore, successful vaccination is key to preventing infection. Vaccination strategies against pneumococcus include a pure polysaccharide vaccine, Pneumovax® (PPV-23), and a polysaccharide-conjugate vaccine, Prevenar-13 ®(PCV-13). PCV-13 is given as part of three vaccine series in infants but is currently recommended only as a single vaccine in adults. The evidence base for either vaccine in adults is limited and guidelines vary. In 2009, national guidelines recommended PPV-23 vaccination but a PCV-13+PPV-23 schedule is now recommended (BHIVA, 2008 & 2015). The Assessment of Immune Responses to Routine Immunisations (AIR) is an observational study that has examined the immune response to UK recommended vaccinations in adults with HIV. Firstly, the AIR study went on to examine the impact of HIV-infection on pneumococcal vaccination with PPV-23, as assessed by pre- and post- vaccine IgG antibodies against 12 pneumococcal (Pn) serotypes (Pn 1, 3, 4, 5, 6B, 7F, 9V, 14,18C, 19A, 19F, and 23F at the WHO (World Health Organization) protective threshold 0.35μg/mL in ≥ 8/12 serotypes threshold using a 19-plex Luminex-based assay. HIV-infected patients responded poorly to a single dose of PPV-23 compared to HIV-negative controls. AIR then established that PCV-13 could increase the percentage of patients that reach WHO protective thresholds compared to a single dose of PPV-23 and that immune responses to PCV-13 could be maintained for a longer period compared to PPV-23. Response rates could be further improved by booster doses of PCV-13. Low antigen-specific IgG concentrations are associated with impaired opsonophagocytic killing against pneumococcus, thus a novel opsonophagocytic assay was developed in order to further understand the relationship between the quantity and opsonic functionality of Pn-specific antibody. Furthermore, assessing responses to pneumococcal vaccination is important in determining immunogenicity. Thus, this thesis also explored the whole vaccine and serotype IgG subclass (IgG1-IgG4) response to PPV-23 and PCV-13 by developing novel Pn-specific IgG subclass assays. Lastly, HIV-infection is characterised by a dysregulated humoral system, therefore, we have examined the impact on different B cell populations at baseline and relationships with total and Pn- specific antibody post-vaccination with PCV-13 are described. In summary, this study aimed to examine the impact of HIV-infection on pneumococcal vaccination by investigating the quantity and quality of the Pn-specific IgG response, IgG subclass responses, and the effects of a dysfunctional humoral system on total and Pn-specific antibody. Findings would be informative in developing vaccination strategies in HIV-infected adults in the UK.
|7 Dec 2018
|Unpublished - 2018