Characterisation of antibody function and B cell repertoire induced by typhoid conjugate vaccine and natural infection of Salmonella Typhi in Malawian children and adults

Typhoid fever is a disease caused by Salmonella Typhi that continues to be a major global health problem. Gaining insights into the host-pathogen interactions is important for disease control and vaccine design. Protective immunity against Salmonella Typhi is thought to be antibody-mediated and this is the basis for they Typhoid Conjugate vaccine. However, the actual correlate of protection is still not well defined. Using samples from an ongoing Typhoid Conjugate Vaccine trial and a study investigating immunity generated by natural S.Typhi infection, we aim to investigate the specificity and functionality of antibodies that are induced post-vaccination and during/following natural S.Typhi infection in Malawian children and adults.

Where does this project lie in the translational pathway?

T1 – Basic Research in Medecine

T2 Human / Clinical Research in Medecine

 

 

Quantitative analysis of immunological parameters (human observational and following a human vaccine intervention) will be used to identify potential correlates of protection to be used for vaccine development

What are the methodological aspects of the PhD project?

The project offers a variety of techniques including tissue culture, antibody quantitative, specificity and functional  assays, cellular immune assays by flow cytometry, microbiology and molecular biology.

What are the expected outputs of the PhD project?

Publications: Would be expected to provide 2 or 3  3/4* REF-returnable papers

Impact: It will provide important information for vaccine development for LMIC’s, and will form part of a much

External industry links or training opportunities available for the student

Link to the Malawi-Liverpool-Wellcome Trust Clinical Research in Medecine programme (MLW)

Required skills/experience/aptitudes

Qualification

MSc in Immunology or equivalent

 

Experience

  1. Experience of working in a LMIC
  2. Hands-on experience with common immunological assays (flow cytometry and ELISA)
  3. Experience with RT-PCR, RNA preparation

 

Skills

  1. Ability to work in a diverse team of basic scientists and clinicians
  2. Enthusiastic approach to work and ability to use initiative and work independently or as part of a team

 

Key publications that relate to this proposed project

1.

Feasey NA, Gaskell K, Wong V, Msefula C, Selemani G,… Gordon M.A, Heyderman R. (2015) Rapid Emergence of Multidrug Resistant, H58-Lineage Salmonella Typhi in Blantyre, Malawi. PLOS Neglected Tropical Diseases 9(4): e0003748.

2.

Pennington, S. H., Thompson, A. L., Wright, A. K. A., Ferreira, D. M., Jambo, K. C., Wright, A. D., … Gordon, M. A. (2016). Oral Typhoid Vaccination With Live-Attenuated Salmonella Typhi Strain Ty21a Generates Ty21a-Responsive and Heterologous Influenza Virus–Responsive CD4+ and CD8+ T Cells at the Human Intestinal Mucosa. The Journal of Infectious Diseases, 213(11), 1809–1819.

3.

Jin, C., Gibani, M. M., Moore, M., Juel, H. B., Jones, E., Meiring, J., … Pollard, A. J. (2017). Efficacy and immunogenicity of a Vi-tetanus toxoid conjugate vaccine in the prevention of typhoid fever using a controlled human infection model of Salmonella Typhi: a randomised controlled, phase 2b trial. Lancet (London, England), 390(10111), 2472–2480. (17)32149-9

4.

Nyirenda, T. S., Nyirenda, J. T., Tembo, D. L., Storm, J., Dube, Q., Msefula, C. L., … Mandala, W. L. (2017). Loss of Humoral and Cellular Immunity to Invasive Nontyphoidal Salmonella during Current or Convalescent Plasmodium falciparum Infection in Malawian Children. Clinical and Vaccine Immunology : CVI, 24(7), e00057–17.

5.

Kovaltsuk, A., Krawczyk, K., Galson, J.D., Kelly, D.F., Deane, C.M., Trück, J. (2017) How B-Cell Receptor Repertoire Sequencing Can Be Enriched with Structural Antibody Data. Frontiers in Immunology 8:1753, ISSN=1664-3224  DOI=10.3389/fimmu.2017.01753

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