Investigation of how antibody to the outer membrane porin d from salmonella typhimurium binds and protects against infection

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Dominguez Medina, Carmen Coral (2018). Investigation of how antibody to the outer membrane porin d from salmonella typhimurium binds and protects against infection. University of Birmingham. Ph.D.

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Abstract

The induction of specific-antibody that targets the surface of a pathogen or its secreted components is the basis of immunological memory to natural infection and vaccination. This antibody, induced after natural infection or vaccination, saves millions of lives every year. The few vaccines against Gram-negative bacteria either target one antigen, the surface capsular polysaccharides, or are complex vaccines involving the whole organism or complex mixtures of multiple antigens. In this project, we studied how antibody binds to the Salmonella outer membrane porin D (STm-OmpD) on the bacterial surface and why it is protective. Immunisation with STmOmpD provides serovar-specific protection because: 1) lgG can access a single epitope, which is under selective pressure; 2) lgG can access the bacterial surface in the "footprint" made by the OmpD trimer; and 3) Lipopolysaccharide (LPS) 0-antigen (0-Ag) influences the access of lgG to epitopes. Further, protection after immunisation with STm-OmpD is detectable by 4 hours after infection and requires GR1+ cells, IFNg, and Th1 responses for optimal protection, but not lgG2a/c. These data provide insights into how antibody to the Gramnegative bacterial surface can help protect against infection and will aid in the optimisation of subunit vaccines targeting Salmonella.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):