Polymeric Pathogen-Like Particles-Based Combination Adjuvants Elicit Potent Mucosal T Cell Immunity to Influenza A Virus
Eliciting durable and protective T cell-mediated immunity in the respiratory mucosa remains a significant challenge. Polylactic-co-glycolic acid (PLGA)-based cationic pathogen-like particles (PLPs) loaded with TLR agonists mimic biophysical properties of microbes and hence, simulate pathogen-pattern...
Main Authors: | , , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Frontiers Media S.A.
2021-03-01
|
Series: | Frontiers in Immunology |
Subjects: | |
Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2020.559382/full |
id |
doaj-67c46005f89f4a50b0ee1e1d7965e5bf |
---|---|
record_format |
Article |
spelling |
doaj-67c46005f89f4a50b0ee1e1d7965e5bf2021-03-09T14:49:11ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-03-011110.3389/fimmu.2020.559382559382Polymeric Pathogen-Like Particles-Based Combination Adjuvants Elicit Potent Mucosal T Cell Immunity to Influenza A VirusBrock Kingstad-Bakke0Randall Toy1Woojong Lee2Pallab Pradhan3Gabriela Vogel4Chandranaik B. Marinaik5Autumn Larsen6Daisy Gates7Tracy Luu8Bhawana Pandey9Yoshihoro Kawaoka10Krishnendu Roy11M. Suresh12Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, WI, United StatesThe Wallace H. Coulter Department of Biomedical Engineering Georgia Institute of Technology and Emory University, Atlanta, GA, United StatesDepartment of Pathobiological Sciences, University of Wisconsin-Madison, Madison, WI, United StatesThe Wallace H. Coulter Department of Biomedical Engineering Georgia Institute of Technology and Emory University, Atlanta, GA, United StatesThe Wallace H. Coulter Department of Biomedical Engineering Georgia Institute of Technology and Emory University, Atlanta, GA, United StatesDepartment of Pathobiological Sciences, University of Wisconsin-Madison, Madison, WI, United StatesDepartment of Pathobiological Sciences, University of Wisconsin-Madison, Madison, WI, United StatesDepartment of Pathobiological Sciences, University of Wisconsin-Madison, Madison, WI, United StatesDepartment of Pathobiological Sciences, University of Wisconsin-Madison, Madison, WI, United StatesThe Wallace H. Coulter Department of Biomedical Engineering Georgia Institute of Technology and Emory University, Atlanta, GA, United StatesDepartment of Pathobiological Sciences, University of Wisconsin-Madison, Madison, WI, United StatesThe Wallace H. Coulter Department of Biomedical Engineering Georgia Institute of Technology and Emory University, Atlanta, GA, United StatesDepartment of Pathobiological Sciences, University of Wisconsin-Madison, Madison, WI, United StatesEliciting durable and protective T cell-mediated immunity in the respiratory mucosa remains a significant challenge. Polylactic-co-glycolic acid (PLGA)-based cationic pathogen-like particles (PLPs) loaded with TLR agonists mimic biophysical properties of microbes and hence, simulate pathogen-pattern recognition receptor interactions to safely and effectively stimulate innate immune responses. We generated micro particle PLPs loaded with TLR4 (glucopyranosyl lipid adjuvant, GLA) or TLR9 (CpG) agonists, and formulated them with and without a mucosal delivery enhancing carbomer-based nanoemulsion adjuvant (ADJ). These adjuvants delivered intranasally to mice elicited high numbers of influenza nucleoprotein (NP)-specific CD8+ and CD4+ effector and tissue-resident memory T cells (TRMs) in lungs and airways. PLPs delivering TLR4 versus TLR9 agonists drove phenotypically and functionally distinct populations of effector and memory T cells. While PLPs loaded with CpG or GLA provided immunity, combining the adjuvanticity of PLP-GLA and ADJ markedly enhanced the development of airway and lung TRMs and CD4 and CD8 T cell-dependent immunity to influenza virus. Further, balanced CD8 (Tc1/Tc17) and CD4 (Th1/Th17) recall responses were linked to effective influenza virus control. These studies provide mechanistic insights into vaccine-induced pulmonary T cell immunity and pave the way for the development of a universal influenza and SARS-CoV-2 vaccines.https://www.frontiersin.org/articles/10.3389/fimmu.2020.559382/fulladjuvantsCD8tissue-resident memoryCD4influenza A virusvaccine |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Brock Kingstad-Bakke Randall Toy Woojong Lee Pallab Pradhan Gabriela Vogel Chandranaik B. Marinaik Autumn Larsen Daisy Gates Tracy Luu Bhawana Pandey Yoshihoro Kawaoka Krishnendu Roy M. Suresh |
spellingShingle |
Brock Kingstad-Bakke Randall Toy Woojong Lee Pallab Pradhan Gabriela Vogel Chandranaik B. Marinaik Autumn Larsen Daisy Gates Tracy Luu Bhawana Pandey Yoshihoro Kawaoka Krishnendu Roy M. Suresh Polymeric Pathogen-Like Particles-Based Combination Adjuvants Elicit Potent Mucosal T Cell Immunity to Influenza A Virus Frontiers in Immunology adjuvants CD8 tissue-resident memory CD4 influenza A virus vaccine |
author_facet |
Brock Kingstad-Bakke Randall Toy Woojong Lee Pallab Pradhan Gabriela Vogel Chandranaik B. Marinaik Autumn Larsen Daisy Gates Tracy Luu Bhawana Pandey Yoshihoro Kawaoka Krishnendu Roy M. Suresh |
author_sort |
Brock Kingstad-Bakke |
title |
Polymeric Pathogen-Like Particles-Based Combination Adjuvants Elicit Potent Mucosal T Cell Immunity to Influenza A Virus |
title_short |
Polymeric Pathogen-Like Particles-Based Combination Adjuvants Elicit Potent Mucosal T Cell Immunity to Influenza A Virus |
title_full |
Polymeric Pathogen-Like Particles-Based Combination Adjuvants Elicit Potent Mucosal T Cell Immunity to Influenza A Virus |
title_fullStr |
Polymeric Pathogen-Like Particles-Based Combination Adjuvants Elicit Potent Mucosal T Cell Immunity to Influenza A Virus |
title_full_unstemmed |
Polymeric Pathogen-Like Particles-Based Combination Adjuvants Elicit Potent Mucosal T Cell Immunity to Influenza A Virus |
title_sort |
polymeric pathogen-like particles-based combination adjuvants elicit potent mucosal t cell immunity to influenza a virus |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2021-03-01 |
description |
Eliciting durable and protective T cell-mediated immunity in the respiratory mucosa remains a significant challenge. Polylactic-co-glycolic acid (PLGA)-based cationic pathogen-like particles (PLPs) loaded with TLR agonists mimic biophysical properties of microbes and hence, simulate pathogen-pattern recognition receptor interactions to safely and effectively stimulate innate immune responses. We generated micro particle PLPs loaded with TLR4 (glucopyranosyl lipid adjuvant, GLA) or TLR9 (CpG) agonists, and formulated them with and without a mucosal delivery enhancing carbomer-based nanoemulsion adjuvant (ADJ). These adjuvants delivered intranasally to mice elicited high numbers of influenza nucleoprotein (NP)-specific CD8+ and CD4+ effector and tissue-resident memory T cells (TRMs) in lungs and airways. PLPs delivering TLR4 versus TLR9 agonists drove phenotypically and functionally distinct populations of effector and memory T cells. While PLPs loaded with CpG or GLA provided immunity, combining the adjuvanticity of PLP-GLA and ADJ markedly enhanced the development of airway and lung TRMs and CD4 and CD8 T cell-dependent immunity to influenza virus. Further, balanced CD8 (Tc1/Tc17) and CD4 (Th1/Th17) recall responses were linked to effective influenza virus control. These studies provide mechanistic insights into vaccine-induced pulmonary T cell immunity and pave the way for the development of a universal influenza and SARS-CoV-2 vaccines. |
topic |
adjuvants CD8 tissue-resident memory CD4 influenza A virus vaccine |
url |
https://www.frontiersin.org/articles/10.3389/fimmu.2020.559382/full |
work_keys_str_mv |
AT brockkingstadbakke polymericpathogenlikeparticlesbasedcombinationadjuvantselicitpotentmucosaltcellimmunitytoinfluenzaavirus AT randalltoy polymericpathogenlikeparticlesbasedcombinationadjuvantselicitpotentmucosaltcellimmunitytoinfluenzaavirus AT woojonglee polymericpathogenlikeparticlesbasedcombinationadjuvantselicitpotentmucosaltcellimmunitytoinfluenzaavirus AT pallabpradhan polymericpathogenlikeparticlesbasedcombinationadjuvantselicitpotentmucosaltcellimmunitytoinfluenzaavirus AT gabrielavogel polymericpathogenlikeparticlesbasedcombinationadjuvantselicitpotentmucosaltcellimmunitytoinfluenzaavirus AT chandranaikbmarinaik polymericpathogenlikeparticlesbasedcombinationadjuvantselicitpotentmucosaltcellimmunitytoinfluenzaavirus AT autumnlarsen polymericpathogenlikeparticlesbasedcombinationadjuvantselicitpotentmucosaltcellimmunitytoinfluenzaavirus AT daisygates polymericpathogenlikeparticlesbasedcombinationadjuvantselicitpotentmucosaltcellimmunitytoinfluenzaavirus AT tracyluu polymericpathogenlikeparticlesbasedcombinationadjuvantselicitpotentmucosaltcellimmunitytoinfluenzaavirus AT bhawanapandey polymericpathogenlikeparticlesbasedcombinationadjuvantselicitpotentmucosaltcellimmunitytoinfluenzaavirus AT yoshihorokawaoka polymericpathogenlikeparticlesbasedcombinationadjuvantselicitpotentmucosaltcellimmunitytoinfluenzaavirus AT krishnenduroy polymericpathogenlikeparticlesbasedcombinationadjuvantselicitpotentmucosaltcellimmunitytoinfluenzaavirus AT msuresh polymericpathogenlikeparticlesbasedcombinationadjuvantselicitpotentmucosaltcellimmunitytoinfluenzaavirus |
_version_ |
1724227690026762240 |