Trained immunity: using controlled human infection to study non-specific beneficial effects of vaccination

This PhD opportunity is being offered as part of the LSTM and Lancaster University Doctoral Training Partnership. Find out more about the studentships and how to apply. 

Abstract

This is an exciting opportunity to work in vaccine development at LSTM. You will be integrated into a dynamic team with a diverse research portfolio, supported by strategic collaborations with world-leading academic (Oxford) and industrial institutions. This project will work towards improving our understanding of how vaccination can confer non-specific beneficial effects. We will work to understand how favourable immune responses may be generated with both specific and non-specific beneficial impact – potentially leading to the development of novel adjuvant formulations and the optimisation of vaccine scheduling. We will study a variety of bacterial and viral pathogens of clinical significance, including Streptococcus pneumoniae, Mycobacterium tuberculosis, Salmonella enterica, SARS, MERS, and RSV. Projects will utilise ex vivo human models of infection, advanced analytical techniques (flow cytometry and confocal microscopy), and systems biology to assess the immunomodulatory impact of controlled human infection and vaccination. Projects will be tailored to the candidate and provide opportunity for industry training and overseas placement.

Where does the project lie on the Translational Pathway?

T1 – Basic Research

T2 Human / Clinical Research

Expected Outputs

Publications as well as proof-of-concept data to support grant applications for further research towards the development of novel adjuvant formulations as well as for optimisation of vaccine scheduling.

Training Opportunities

Training in the generation of advanced ex vivo organoid infection models using primary human cells.

 

Practical training in use of the following advanced analytical platforms:

  1. Flow cytometry
  2. High-content confocal imaging
  3. qPCR

 

Training in the following quantitative methods:

  1. Statistical analyses
  2. Bioinformatics
  3. Systems biology

Skills Required

Interest in immunology and vaccination with ambition to change clinical practice to improve quality of life globally.

Key Publications associated with this project

Pennington SH, Ferreira DM, Caamaño-Gutiérrez E, Reiné J, Hewitt C, Hyder-Wright AD, Gordon SB, Gordon MA. Nonspecific effects of oral vaccination with live-attenuated Salmonella Typhi strain Ty21a. Sci Adv. 2019 Feb 27;5(2):eaau6849. doi: 10.1126/sciadv.aau6849. PMID: 30820452; PMCID: PMC6392763.

Pennington SH, Pojar S, Mitsi E, Gritzfeld JF, Nikolaou E, Solórzano C, Owugha JT, Masood Q, Gordon MA, Wright AD, Collins AM, Miyaji EN, Gordon SB, Ferreira DM. Polysaccharide-Specific Memory B Cells Predict Protection against Experimental Human Pneumococcal Carriage. Am J Respir Crit Care Med. 2016 Dec 15;194(12):1523-1531. doi: 10.1164/rccm.201512-2467OC. PMID: 27403678; PMCID: PMC5215029.

Stuart ASV, Shaw RH, Liu X, Greenland M, Aley PK, Andrews NJ, Cameron JC, Charlton S, Clutterbuck EA, Collins AM, Darton T, Dinesh T, Duncan CJA, England A, Faust SN, Ferreira DM, Finn A, Goodman AL, Green CA, Hallis B, Heath PT, Hill H, Horsington BM, Lambe T, Lazarus R, Libri V, Lillie PJ, Mujadidi YF, Payne R, Plested EL, Provstgaard-Morys S, Ramasamy MN, Ramsay M, Read RC, Robinson H, Screaton GR, Singh N, Turner DPJ, Turner PJ, Vichos I, White R, Nguyen-Van-Tam JS, Snape MD; Com-COV2 Study Group. Immunogenicity, safety, and reactogenicity of heterologous COVID-19 primary vaccination incorporating mRNA, viral-vector, and protein-adjuvant vaccines in the UK (Com-COV2): a single-blind, randomised, phase 2, non-inferiority trial. Lancet. 2022 Jan 1;399(10319):36-49. doi: 10.1016/S0140-6736(21)02718-5. Epub 2021 Dec 6. Erratum in: Lancet. 2022 Feb 26;399(10327):802. PMID: 34883053; PMCID: PMC8648333.

Voysey M, Costa Clemens SA, Madhi SA, Weckx LY, Folegatti PM, Aley PK, Angus B, Baillie VL, Barnabas SL, Bhorat QE, Bibi S, Briner C, Cicconi P, Clutterbuck EA, Collins AM, Cutland CL, Darton TC, Dheda K, Dold C, Duncan CJA, Emary KRW, Ewer KJ, Flaxman A, Fairlie L, Faust SN, Feng S, Ferreira DM, Finn A, Galiza E, Goodman AL, Green CM, Green CA, Greenland M, Hill C, Hill HC, Hirsch I, Izu A, Jenkin D, Joe CCD, Kerridge S, Koen A, Kwatra G, Lazarus R, Libri V, Lillie PJ, Marchevsky NG, Marshall RP, Mendes AVA, Milan EP, Minassian AM, McGregor A, Mujadidi YF, Nana A, Padayachee SD, Phillips DJ, Pittella A, Plested E, Pollock KM, Ramasamy MN, Ritchie AJ, Robinson H, Schwarzbold AV, Smith A, Song R, Snape MD, Sprinz E, Sutherland RK, Thomson EC, Török ME, Toshner M, Turner DPJ, Vekemans J, Villafana TL, White T, Williams CJ, Douglas AD, Hill AVS, Lambe T, Gilbert SC, Pollard AJ; Oxford COVID Vaccine Trial Group. Single-dose administration and the influence of the timing of the booster dose on immunogenicity and efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine: a pooled analysis of four randomised trials. Lancet. 2021 Mar 6;397(10277):881-891. doi: 10.1016/S0140-6736(21)00432-3. Epub 2021 Feb 19. Erratum in: Lancet. 2021 Mar 6;397(10277):880. PMID: 33617777; PMCID: PMC7894131.

Voysey M, Costa Clemens SA, Madhi SA, Weckx LY, Folegatti PM, Aley PK, Angus B, Baillie VL, Barnabas SL, Bhorat QE, Bibi S, Briner C, Cicconi P, Clutterbuck EA, Collins AM, Cutland CL, Darton TC, Dheda K, Dold C, Duncan CJA, Emary KRW, Ewer KJ, Flaxman A, Fairlie L, Faust SN, Feng S, Ferreira DM, Finn A, Galiza E, Goodman AL, Green CM, Green CA, Greenland M, Hill C, Hill HC, Hirsch I, Izu A, Jenkin D, Joe CCD, Kerridge S, Koen A, Kwatra G, Lazarus R, Libri V, Lillie PJ, Marchevsky NG, Marshall RP, Mendes AVA, Milan EP, Minassian AM, McGregor A, Mujadidi YF, Nana A, Padayachee SD, Phillips DJ, Pittella A, Plested E, Pollock KM, Ramasamy MN, Ritchie AJ, Robinson H, Schwarzbold AV, Smith A, Song R, Snape MD, Sprinz E, Sutherland RK, Thomson EC, Török ME, Toshner M, Turner DPJ, Vekemans J, Villafana TL, White T, Williams CJ, Douglas AD, Hill AVS, Lambe T, Gilbert SC, Pollard AJ; Oxford COVID Vaccine Trial Group. Single-dose administration and the influence of the timing of the booster dose on immunogenicity and efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine: a pooled analysis of four randomised trials. Lancet. 2021 Mar 6;397(10277):881-891. doi: 10.1016/S0140-6736(21)00432-3. Epub 2021 Feb 19. Erratum in: Lancet. 2021 Mar 6;397(10277):880. PMID: 33617777; PMCID: PMC7894131.