Details

Autor(en) / Beteiligte

• Rabquer, Bradley J

Titel

The immune response to Streptococcus pneumoniae and pneumococcal polysaccharides

Ort / Verlag

ProQuest Dissertations & Theses

Erscheinungsjahr

2006

Quelle

ProQuest Dissertations & Theses A&I

Beschreibungen/Notizen

• Streptococcus pneumoniae is a worldwide pathogen that colonizes the human nasopharynx. Pneumococcal vaccines have been developed which exploit the major virulence factor of S. pneumoniae, the capsular polysaccharide (PPS). Recently, research has begun to examine the variable region repertoire elicited by PPS vaccination in order to understand the structure-function relationship of anti-PPS antibodies. The majority of these studies have isolated PPS-specific B cells seven days post-vaccination, when PPS-specific B cells are most abundant. These studies have revealed restricted variable gene usage and considerable somatic mutations, indicative of a memory response. Although the mechanism of hypermutation produced in response to T cell independent (TI) antigens such as PPS remains to elucidated, somatic hypermutation continues to increase past seven days post-vaccination in response to T cell dependent (TD) antigens. Moreover, it has not been demonstrated that isolating PPS-specific B cells at seven days post-vaccination reflects long-term protective serum anti-PPS antibodies. We hypothesized that B cells isolated between 4-6 weeks post-vaccination reflect the physiologically relevant serum antibody response. Our results demonstrated differential variable gene usage between PPS-specific B cells isolated at 5-10 days and 4-6 weeks post-vaccination. In addition, light chain isotype analysis suggested that PPS-specific B cells isolated 5-10 days post-vaccination reflect the serum anti-PPS antibody at both 5-10 days and 4-6 weeks post-vaccination. Therefore, PPS-specific B cells should be isolated at 5-10 days post-vaccination for variable gene analysis. Moreover, the variable regions isolated at 5-10 days contained significant somatic mutations, indicative of a memory response. Concurrently, the majority of adults had anti-PPS antibody present prior to vaccination. Previous studies have indicated that previous exposure to polysaccharide antigen can affect subsequent polysaccharide-based vaccination. We therefore hypothesized that priming with PPS affects the subsequent immune response to vaccination. Our studies indicate that while prior vaccination with PPS does not affect subsequent vaccination with the pneumococcal conjugate vaccine (CPV), live colonization with S. pneumoniae enhances the magnitude of the response via a B cell dependent mechanism. These results demonstrate the importance of prior immunologic exposure on CPV vaccination, and that stimulation of the mucosal immune system may be advantageous prior to vaccination.