Oxford University Clinical Research Unit Vietnam PhD Programme 2014-15
Project 5:
The mechanism of antibody activity during Salmonella Typhi and Salmonella Paratyphi A infections
Required person: Basic laboratory scientist/bioinformatician/immunologist
Type of project: Bacteriology/immunology
Potential start date: First quarter 2015
Duration: Four years
Techniques: Immunology, bacteriology, diagnostics, molecular biology
Location: Ho Chi Minh City, Vietnam, The Wellcome Trust Sanger Institute, Cambridge UK
Group: Enteric Infections
Supervisor: Guy Thwaites, Gordon Dougan, Stephen Baker
Current status: Ethical approval obtained, funded, publication
Collaborations: Oxford University – UK, Oxford University Clinical Research Unit – Nepal, The Wellcome Trust Sanger Institute, Cambridge UK
Brief outline
Salmonella Paratyphi A is a largely understudied cause of enteric fever, and in some locations is replacing Salmonella Typhi as the major cause of bacteremia. Currently there are limited data on clinical response to therapy, phylogeny or specific immunological responses to Salmonella Paratyphi A and Salmonella Typhi during and after acute infection. However, we know that antibody responses to classical invasive Salmonella antigens (O-antigen Vi) are induced during acute enteric fever and such responses likely contribute to immunity (as indicated by data from both immunization and natural history of disease). Consequently, we hypothesize that additional antigen specific antibody responses, which are induced during enteric fever, are important for homotypic and heterotypic (Typhi and Paratyphi A) immunity and for stimulating bacteriocidal killing.
Potential thesis areas
- Analysis of the serological response to Typhi/Paratyphi A antigens
- The bactericidal activity against novel Typhi/Paratyphi A antigens
- Using Typhi/Para A TraDis libraries to identify antigens that are targeted during the bactericidal response
- The Mechanism of the bactericidal response induced by specific antibody responses during a Typhi/Para A infection
Associated group publications
Harris JB, Larocque RC, Calderwood SB, Qadri F, Felgner PL, Ryan ET.
Immunoproteomic analysis of antibody in lymphocyte supernatant in patients with
typhoid fever in Bangladesh. Clin Vaccine Immunol. 2014 Mar;21(3):280-5. doi:
10.1128/CVI.00661-13. Epub 2013 Dec 26. PubMed PMID: 24371257; PubMed Central
PMCID: PMC3957676.
2: Liang L, Juarez S, Nga TV, Dunstan S, Nakajima-Sasaki R, Davies DH, McSorley
S, Baker S, Felgner PL. Immune profiling with a Salmonella Typhi antigen
microarray identifies new diagnostic biomarkers of human typhoid. Sci Rep.
2013;3:1043. doi: 10.1038/srep01043. Epub 2013 Jan 9. PubMed PMID: 23304434;
PubMed Central PMCID: PMC3540400.
