MAIT cell activation augments adenovirus vector vaccine immunogenicity

10.1126/science.aax8819

Science

4th February 2021

Contributing to research themes:

Mucosal-associated invariant T (MAIT) cells are innate sensors of viruses and can augment early immune responses and contribute to protection. We hypothesized that MAIT cells may have inherent adjuvant activity in vaccine platforms that use replication-incompetent adenovirus vectors. In mice and humans, ChAdOx1 (chimpanzee adenovirus Ox1) immunization robustly activated MAIT cells. Activation required plasmacytoid dendritic cell (pDC)–derived interferon (IFN)–α and monocyte-derived interleukin-18. IFN-α–induced, monocyte-derived tumor necrosis factor was also identified as a key secondary signal. All three cytokines were required in vitro and in vivo. Activation of MAIT cells positively correlated with vaccine-induced T cell responses in human volunteers and MAIT cell–deficient mice displayed impaired CD8+ T cell responses to multiple vaccine-encoded antigens. Thus, MAIT cells contribute to the immunogenicity of adenovirus vectors, with implications for vaccine design.

Author list:

Nicholas M Provine 1, Ali Amini 2, Lucy C Garner 2, Alexandra J Spencer 3, Christina Dold 4, Claire Hutchings 5, Laura Silva Reyes 4, Michael E B FitzPatrick 2, Senthil Chinnakannan 5, Blanche Oguti 4, Meriel Raymond 4, Marta Ulaszewska 3, Fulvia Troise 6 7, Hannah Sharpe 3, Sophie B Morgan 8 Timothy S C Hinks 8, Teresa Lambe 3, Stefania Capone 9, Antonella Folgori 9, Eleanor Barnes 2 3 5, Christine S Rollier 4, Andrew J Pollard 4, Paul Klenerman 1 5

 

1. Translational Gastroenterology Unit, Nuffield Department of Medicine, University of Oxford, Oxford, UK. nicholas.provine@ndm.ox.ac.uk paul.klenerman@ndm.ox.ac.uk.

2. Translational Gastroenterology Unit, Nuffield Department of Medicine, University of Oxford, Oxford, UK.

3. Jenner Institute, University of Oxford, Oxford, UK.

4. Oxford Vaccine Group, Department of Paediatrics, University of Oxford, and the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre, Oxford, UK.

5. Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK.

6. Nouscom, SRL, Rome, Italy.

7. Ceinge Biotechnologie Avanzate, Naples, Italy.

8. Respiratory Medicine Unit, Nuffield Department of Medicine - Experimental Medicine, University of Oxford, Oxford, UK.

9. ReiThera, SRL, Rome, Italy.