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The Microbiome and Vaccine Response

  • Project No: KTPS-NC-7
  • Intake: 2021 KTPS-NC

PROJECT OUTLINE

The human gut harbours a complex microbial ecosystem that can influence many aspects of host physiology and plays an important role in shaping the host immune system. Emerging evidence points to a key role for the gut microbiome in controlling responses to immunotherapy and improving vaccine-induced immunity. This suggested the potential of manipulating the intestinal microbiome for therapeutic goals.

The aim of this project is to understand and exploit the ability of commensal gut microbes to influence the human immune response to viral vectored vaccines, based on the ability of microbes to either directly, or indirectly modulate CD8+ T cells.

This is an interdisciplinary project that will begin by combining clinical trials of prophylactic and therapeutic vaccines against viral infections (e.g HIV and HBV) with in-depth multi-omic analysis to identify functional variation in the gut microbiome associated with immunological markers of vaccine response. It will progress to investigating the potential of specific microbes (or microbial products) as adjuvants to improve vaccine-induced immunity.

KEYWORDS

Vaccination, Microbiome, Metagenomics, T Cells, HIV

TRAINING OPPORTUNITIES

This position will be based within the Oxford Centre for Microbiome Studies at the Kennedy Institute for Rheumatology and The Jenner Institute. Together these institutes combine state-of-the art facilities for microbiome research with world-class expertise in immunology and vaccine development.

The successful applicant will gain experience of working alongside established clinical trials of viral vaccines. They will also receive the computational and laboratory training necessary to generate, analyse and interpret large multi-omic datasets (shotgun metagenomics, metabolomics).  They will be expected to publish results in peer-reviewed journals and present at national and international scientific conferences.

As well as institutional support, the successful applicant will benefit from being part of the University of Oxford college system.

KEY PUBLICATIONS

  1. de Jong SE, Olin A, Pulendran B (2020) The Impact of the Microbiome on Immunity to Vaccination in Humans. Cell Host and Microbe, 28:2, 169-179.
  2. SahBandar IN, Chew GM, Corley MJ, Pang APS, Tsai N, Hanks N, Khadka VS, Klatt NR, Hensley-McBain T, Somsouk M, Vujkovic-Cvijin I, Chow DC, Shikuma CM, Ndhlovu LC (2020) Changes in gastrointestinal microbial communities influence HIV-specific CD8+ T-cell responsiveness to immune checkpoint blockade. AIDS, 34, 1451-1460
  3. Hanke T (2019) Aiming for protective T-cell responses: a focus on the first generation conserved-region HIVconsv vaccines in preventive and therapeutic clinical trials. Expert Review of Vaccines, 18:10, 1029-1041
  4. Humphries  A (2018) The gut microbiota and immune checkpoint inhibitors. Human Vaccines & Immunotherapeutics, 14:9, 2178-2182
  5. Rooks M, Garrett W (2016) Gut microbiota, metabolites and host immunity. Nature Reviews Immunology, 16, 341-352

THEMES

Vaccines, Microbiome, Immunology

CONTACT INFORMATION OF ALL SUPERVISORS

jethro.johnson@kennedy.ox.ac.uk

paola.cicconi@ndm.ox.ac.uk

mark.coles2@kennedy.ox.ac.uk

claire.pearson@kennedy.ox.ac.uk