MAIT cells activate dendritic cells to promote TFH cell differentiation and induce humoral immunity
Theresa E. Pankhurst,
Kaitlin H. Buick,
Joshua L. Lange,
Andrew J. Marshall,
Kaileen R. Button,
Olga R. Palmer,
Kathryn J. Farrand,
Isabelle Montgomerie,
Thomas W. Bird,
Ngarangi C. Mason,
Joanna Kuang,
Benjamin J. Compton,
Davide Comoletti,
Mariolina Salio,
Vincenzo Cerundolo,
Miguel E. Quiñones-Mateu,
Gavin F. Painter,
Ian F. Hermans,
Lisa M. Connor
Affiliations
Theresa E. Pankhurst
School of Biological Sciences, Victoria University of Wellington, Wellington 6012, New Zealand; Malaghan Institute of Medical Research, Wellington 6242, New Zealand
Kaitlin H. Buick
School of Biological Sciences, Victoria University of Wellington, Wellington 6012, New Zealand; Malaghan Institute of Medical Research, Wellington 6242, New Zealand
Joshua L. Lange
Malaghan Institute of Medical Research, Wellington 6242, New Zealand
Andrew J. Marshall
Ferrier Research Institute, Victoria University of Wellington, Wellington 6012, New Zealand
Kaileen R. Button
School of Biological Sciences, Victoria University of Wellington, Wellington 6012, New Zealand
Olga R. Palmer
Malaghan Institute of Medical Research, Wellington 6242, New Zealand
Kathryn J. Farrand
Malaghan Institute of Medical Research, Wellington 6242, New Zealand
Isabelle Montgomerie
School of Biological Sciences, Victoria University of Wellington, Wellington 6012, New Zealand
Thomas W. Bird
School of Biological Sciences, Victoria University of Wellington, Wellington 6012, New Zealand
Ngarangi C. Mason
Malaghan Institute of Medical Research, Wellington 6242, New Zealand
Joanna Kuang
Department of Microbiology and Immunology, University of Otago, Dunedin 9016, New Zealand
Benjamin J. Compton
Ferrier Research Institute, Victoria University of Wellington, Wellington 6012, New Zealand
Davide Comoletti
School of Biological Sciences, Victoria University of Wellington, Wellington 6012, New Zealand
Mariolina Salio
Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK
Vincenzo Cerundolo
Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK
Miguel E. Quiñones-Mateu
Department of Microbiology and Immunology, University of Otago, Dunedin 9016, New Zealand
Gavin F. Painter
Ferrier Research Institute, Victoria University of Wellington, Wellington 6012, New Zealand
Ian F. Hermans
Malaghan Institute of Medical Research, Wellington 6242, New Zealand
Lisa M. Connor
School of Biological Sciences, Victoria University of Wellington, Wellington 6012, New Zealand; Malaghan Institute of Medical Research, Wellington 6242, New Zealand; Corresponding author
Summary: Protective immune responses against respiratory pathogens, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza virus, are initiated by the mucosal immune system. However, most licensed vaccines are administered parenterally and are largely ineffective at inducing mucosal immunity. The development of safe and effective mucosal vaccines has been hampered by the lack of a suitable mucosal adjuvant. In this study we explore a class of adjuvant that harnesses mucosal-associated invariant T (MAIT) cells. We show evidence that intranasal immunization of MAIT cell agonists co-administered with protein, including the spike receptor binding domain from SARS-CoV-2 virus and hemagglutinin from influenza virus, induce protective humoral immunity and immunoglobulin A production. MAIT cell adjuvant activity is mediated by CD40L-dependent activation of dendritic cells and subsequent priming of T follicular helper cells. In summary, we show that MAIT cells are promising vaccine targets that can be utilized as cellular adjuvants in mucosal vaccines.
