PMID- 33767689
OWN - NLM
STAT- MEDLINE
DCOM- 20210412
LR  - 20220716
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 11
DP  - 2020
TI  - Polymeric Pathogen-Like Particles-Based Combination Adjuvants Elicit Potent 
      Mucosal T Cell Immunity to Influenza A Virus.
PG  - 559382
LID - 10.3389/fimmu.2020.559382 [doi]
LID - 559382
AB  - 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 (T(RM)s) 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 T(RM)s 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.
CI  - Copyright (c) 2021 Kingstad-Bakke, Toy, Lee, Pradhan, Vogel, Marinaik, Larsen, 
      Gates, Luu, Pandey, Kawaoka, Roy and Suresh.
FAU - Kingstad-Bakke, Brock
AU  - Kingstad-Bakke B
AD  - Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, 
      WI, United States.
FAU - Toy, Randall
AU  - Toy R
AD  - The Wallace H. Coulter Department of Biomedical Engineering Georgia Institute of 
      Technology and Emory University, Atlanta, GA, United States.
FAU - Lee, Woojong
AU  - Lee W
AD  - Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, 
      WI, United States.
FAU - Pradhan, Pallab
AU  - Pradhan P
AD  - The Wallace H. Coulter Department of Biomedical Engineering Georgia Institute of 
      Technology and Emory University, Atlanta, GA, United States.
FAU - Vogel, Gabriela
AU  - Vogel G
AD  - The Wallace H. Coulter Department of Biomedical Engineering Georgia Institute of 
      Technology and Emory University, Atlanta, GA, United States.
FAU - Marinaik, Chandranaik B
AU  - Marinaik CB
AD  - Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, 
      WI, United States.
FAU - Larsen, Autumn
AU  - Larsen A
AD  - Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, 
      WI, United States.
FAU - Gates, Daisy
AU  - Gates D
AD  - Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, 
      WI, United States.
FAU - Luu, Tracy
AU  - Luu T
AD  - Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, 
      WI, United States.
FAU - Pandey, Bhawana
AU  - Pandey B
AD  - The Wallace H. Coulter Department of Biomedical Engineering Georgia Institute of 
      Technology and Emory University, Atlanta, GA, United States.
FAU - Kawaoka, Yoshihoro
AU  - Kawaoka Y
AD  - Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, 
      WI, United States.
FAU - Roy, Krishnendu
AU  - Roy K
AD  - The Wallace H. Coulter Department of Biomedical Engineering Georgia Institute of 
      Technology and Emory University, Atlanta, GA, United States.
FAU - Suresh, M
AU  - Suresh M
AD  - Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, 
      WI, United States.
LA  - eng
GR  - R21 AI149793/AI/NIAID NIH HHS/United States
GR  - U01 AI124270/AI/NIAID NIH HHS/United States
GR  - U01 AI124299/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20210304
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Adjuvants, Immunologic)
RN  - 0 (Toll-Like Receptor 4)
RN  - 1SIA8062RS (Polylactic Acid-Polyglycolic Acid Copolymer)
SB  - IM
MH  - Adjuvants, Immunologic/*pharmacology
MH  - Animals
MH  - Cell Line
MH  - Dogs
MH  - Immunity, Cellular/*immunology
MH  - Immunity, Innate/immunology
MH  - Immunologic Memory/immunology
MH  - Influenza A virus/*immunology
MH  - Intraepithelial Lymphocytes/*immunology
MH  - Lung/immunology/virology
MH  - Madin Darby Canine Kidney Cells
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Orthomyxoviridae Infections/immunology
MH  - Polylactic Acid-Polyglycolic Acid Copolymer/immunology
MH  - Toll-Like Receptor 4/immunology
PMC - PMC7986715
OTO - NOTNLM
OT  - CD4
OT  - CD8
OT  - adjuvants
OT  - influenza A virus
OT  - polyfunctional
OT  - tissue-resident memory
OT  - vaccine
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2021/03/27 06:00
MHDA- 2021/04/13 06:00
PMCR- 2021/03/04
CRDT- 2021/03/26 06:56
PHST- 2020/05/06 00:00 [received]
PHST- 2020/12/21 00:00 [accepted]
PHST- 2021/03/26 06:56 [entrez]
PHST- 2021/03/27 06:00 [pubmed]
PHST- 2021/04/13 06:00 [medline]
PHST- 2021/03/04 00:00 [pmc-release]
AID - 10.3389/fimmu.2020.559382 [doi]
PST - epublish
SO  - Front Immunol. 2021 Mar 4;11:559382. doi: 10.3389/fimmu.2020.559382. eCollection 
      2020.