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Characterisation of a novel heat shock protein-enriched multivalent Streptococcus pneumoniae protein antigen vaccine

Chan, SW; (2016) Characterisation of a novel heat shock protein-enriched multivalent Streptococcus pneumoniae protein antigen vaccine. Doctoral thesis , UCL (University College London).

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Abstract

Current vaccination against Streptococcus pneumoniae uses vaccines based on capsular polysaccharides from a limited number of serotypes, which has led to replacement by non-vaccine serotypes. An alternative approach based on multiple protein antigens enriched with and bound to highly conserved heat-shock proteins (Hsps) could provide multivalent protection, thereby preventing the problem of serotype replacement. The work in this thesis using proteomic techniques shows that the Hsp vaccine preparation resulted in a product that was enriched with Hsps and contained several known important antigens. The Hsp vaccine induced robust antibody responses in rodents and serum from vaccinated animals contained cross-reactive antibodies against multiple serotypes, including non-vaccine serotypes. Homologous and heterologous strains of S. pneumoniae were opsonised with Hsp vaccine-induced IgG. In mouse models of active vaccination significantly protected against pneumonia infection whilst passive vaccination of rabbit serum significantly protected against sepsis caused by both the homologous and a heterologous S. pneumoniae strain. These data suggest that the Hsp vaccine has the potential to provide serotype-independent protection against S. pneumoniae. Further work in this thesis also showed that protective immunity induced by prior exposure to S. pneumoniae, either by intraperitoneal injection of killed bacteria or by colonisation with live bacteria, targeted protein antigens and was enhanced by exposure to multiple S. pneumoniae strains. In particular, immunisation with multiple strains induced broader cross-reactive immunity to heterologous strains than exposure to only a single strain. This offers insight into how naturally acquired immunity to multiple S. pneumoniae strains develops in humans, and suggests that vaccines derived from multiple strains will provide stronger heterologous protection.

Type: Thesis (Doctoral)
Title: Characterisation of a novel heat shock protein-enriched multivalent Streptococcus pneumoniae protein antigen vaccine
Event: UCL (University College London)
Language: English
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
URI: http://discovery.ucl.ac.uk/id/eprint/1524189
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