The role of antibody in cell-mediated immunity to Non-typhoidal Salmonella in African children and HIV-infected adults.

Nontyphoidal Salmonella (NTS) are a major cause of invasive disease in young children and HIV-infected adults in Sub-Saharan Africa. To develop a vaccine for NTS, an improved understanding of immunity to NTS is required. This thesis investigates the role of opsonic antibody in protection against NTS. First, we defined the optimal serum handling conditions to preserve complement function. We determined minimal titres of antibody and complement required for cell-mediated killing of Salmonella and found they are higher than for cell-free killing. We demonstrated impaired blood cell killing of NTS opsonised with sera from HIV-infected Africans. Developing a method to purify anti-LPS antibodies, we showed that high titres of anti-LPS antibodies in these sera inhibit cell-mediated killing while lower titres are opsonic and induce cell-mediated killing of NTS. For most children, antibody acquired during NTS bacteraemia effected cell-mediated killing of NTS. High antibody titres were not necessarily protective, but for some sera, dilution prior to opsonisation, induced killing. The sensitivity of Malawian NTS isolates to opsonic antibody varied, with resistance to cell-mediated and bactericidal killing correlating. Overall, this thesis emphasises the importance of opsonic antibody in protecting against NTS and supports the development of a vaccine which induces antibody to Salmonella