tetano
Editor, Senior Moderator
Cell Rep
. 2023 Mar 28;42(4):112310.
doi: 10.1016/j.celrep.2023.112310. Online ahead of print.
MAIT cells activate dendritic cells to promote T[SUB]FH[/SUB] cell differentiation and induce humoral immunity
Theresa E Pankhurst[SUP] 1 [/SUP], Kaitlin H Buick[SUP] 1 [/SUP], Joshua L Lange[SUP] 2 [/SUP], Andrew J Marshall[SUP] 3 [/SUP], Kaileen R Button[SUP] 4 [/SUP], Olga R Palmer[SUP] 2 [/SUP], Kathryn J Farrand[SUP] 2 [/SUP], Isabelle Montgomerie[SUP] 4 [/SUP], Thomas W Bird[SUP] 4 [/SUP], Ngarangi C Mason[SUP] 2 [/SUP], Joanna Kuang[SUP] 5 [/SUP], Benjamin J Compton[SUP] 3 [/SUP], Davide Comoletti[SUP] 4 [/SUP], Mariolina Salio[SUP] 6 [/SUP], Vincenzo Cerundolo[SUP] 6 [/SUP], Miguel E Quiñones-Mateu[SUP] 5 [/SUP], Gavin F Painter[SUP] 3 [/SUP], Ian F Hermans[SUP] 2 [/SUP], Lisa M Connor[SUP] 7 [/SUP]
Affiliations
Abstract
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.
Keywords: CP: Immunology; IgA; MAIT cell; SARS-CoV-2; T(FH) cell; adjuvant; dendritic cell; humoral immunity; influenza; mucosal vaccine.
. 2023 Mar 28;42(4):112310.
doi: 10.1016/j.celrep.2023.112310. Online ahead of print.
MAIT cells activate dendritic cells to promote T[SUB]FH[/SUB] cell differentiation and induce humoral immunity
Theresa E Pankhurst[SUP] 1 [/SUP], Kaitlin H Buick[SUP] 1 [/SUP], Joshua L Lange[SUP] 2 [/SUP], Andrew J Marshall[SUP] 3 [/SUP], Kaileen R Button[SUP] 4 [/SUP], Olga R Palmer[SUP] 2 [/SUP], Kathryn J Farrand[SUP] 2 [/SUP], Isabelle Montgomerie[SUP] 4 [/SUP], Thomas W Bird[SUP] 4 [/SUP], Ngarangi C Mason[SUP] 2 [/SUP], Joanna Kuang[SUP] 5 [/SUP], Benjamin J Compton[SUP] 3 [/SUP], Davide Comoletti[SUP] 4 [/SUP], Mariolina Salio[SUP] 6 [/SUP], Vincenzo Cerundolo[SUP] 6 [/SUP], Miguel E Quiñones-Mateu[SUP] 5 [/SUP], Gavin F Painter[SUP] 3 [/SUP], Ian F Hermans[SUP] 2 [/SUP], Lisa M Connor[SUP] 7 [/SUP]
Affiliations
- PMID: 36989114
- PMCID: PMC10045373
- DOI: 10.1016/j.celrep.2023.112310
Abstract
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.
Keywords: CP: Immunology; IgA; MAIT cell; SARS-CoV-2; T(FH) cell; adjuvant; dendritic cell; humoral immunity; influenza; mucosal vaccine.