PMID- 30448064
OWN - NLM
STAT- MEDLINE
DCOM- 20190603
LR  - 20190603
IS  - 1873-2518 (Electronic)
IS  - 0264-410X (Linking)
VI  - 36
IP  - 52
DP  - 2018 Dec 18
TI  - Characterization of the innate stimulatory capacity of plant-derived virus-like 
      particles bearing influenza hemagglutinin.
PG  - 8028-8038
LID - S0264-410X(18)31496-8 [pii]
LID - 10.1016/j.vaccine.2018.10.099 [doi]
AB  - Cell-mediated immunity is an important component of immediate and long-term 
      anti-viral protection. Dendritic cells (DCs) are essential for the induction of 
      cell-mediated immunity by instructing the activation and differentiation of 
      antigen-specific T cell responses. Activated DCs that express co-stimulatory 
      molecules and pro-inflammatory cytokines are necessary to promote the development 
      of type 1 immune responses required for viral control. Here we report that 
      plant-derived virus-like particles (VLPs) bearing influenza hemagglutinins (HA) 
      directly stimulate mouse and human DCs. DCs exposed to H1- and, to a lesser 
      extent, H5-VLPs in vitro rapidly express co-stimulatory molecules and produce 
      pro-inflammatory cytokines including IL-12, IL-6 and TNFalpha. Furthermore, these 
      VLPs support the activation and differentiation of antigen-specific T cell 
      responses. Mechanistically, H1-VLPs stimulate the activation of kinases typically 
      activated downstream of pattern recognition receptors including AKT, p38, and 
      p42/44 ERK. In vivo, immunization with plant-derived VLPs induce the accumulation 
      of both cDC1s and cDC2 in the draining lymph node and a corresponding increase in 
      T and B cells. VLPs devoid of HA protein activate DCs, suggesting they are 
      intrinsically immunostimulatory. Together, the results demonstrate that these 
      candidate plant-derived VLP vaccines have an inherent and direct stimulatory 
      effect on DCs and can enhance the ability of DCs to promote Type 1 immune 
      responses.
CI  - Copyright (c) 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.
FAU - Won, So-Yoon
AU  - Won SY
AD  - Departments of Physiology and Microbiology & Immunology, Goodman Cancer Research 
      Center, 3655 Promenade Sir William Osler, Montreal, Quebec H3G 1Y6, Canada.
FAU - Hunt, Kristin
AU  - Hunt K
AD  - Departments of Physiology and Microbiology & Immunology, Goodman Cancer Research 
      Center, 3655 Promenade Sir William Osler, Montreal, Quebec H3G 1Y6, Canada.
FAU - Guak, Hannah
AU  - Guak H
AD  - Departments of Physiology and Microbiology & Immunology, Goodman Cancer Research 
      Center, 3655 Promenade Sir William Osler, Montreal, Quebec H3G 1Y6, Canada.
FAU - Hasaj, Benedeta
AU  - Hasaj B
AD  - Departments of Physiology and Microbiology & Immunology, Goodman Cancer Research 
      Center, 3655 Promenade Sir William Osler, Montreal, Quebec H3G 1Y6, Canada.
FAU - Charland, Nathalie
AU  - Charland N
AD  - Medicago Inc., 1020 route de l'Eglise, suite 600, Quebec, Quebec G1V 3V9, Canada.
FAU - Landry, Nathalie
AU  - Landry N
AD  - Medicago Inc., 1020 route de l'Eglise, suite 600, Quebec, Quebec G1V 3V9, Canada.
FAU - Ward, Brian J
AU  - Ward BJ
AD  - Research Institute of the McGill University Health Centre, 1001 Decarie Street, 
      Montreal, Quebec H4A 3J1, Canada.
FAU - Krawczyk, Connie M
AU  - Krawczyk CM
AD  - Departments of Physiology and Microbiology & Immunology, Goodman Cancer Research 
      Center, 3655 Promenade Sir William Osler, Montreal, Quebec H3G 1Y6, Canada. 
      Electronic address: connie.krawczyk@mcgill.ca.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20181114
PL  - Netherlands
TA  - Vaccine
JT  - Vaccine
JID - 8406899
RN  - 0 (Hemagglutinin Glycoproteins, Influenza Virus)
RN  - 0 (Influenza Vaccines)
RN  - 0 (Vaccines, Virus-Like Particle)
SB  - IM
MH  - Animals
MH  - CD4-Positive T-Lymphocytes/immunology
MH  - CD8-Positive T-Lymphocytes/immunology
MH  - Dendritic Cells/*immunology
MH  - Female
MH  - Hemagglutinin Glycoproteins, Influenza Virus/genetics/*immunology
MH  - Humans
MH  - *Immunity, Cellular
MH  - Influenza Vaccines/administration & dosage/*immunology
MH  - Influenza, Human/immunology/prevention & control
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Orthomyxoviridae Infections/immunology/prevention & control
MH  - Plants/genetics/immunology
MH  - Th1 Cells/immunology
MH  - Vaccines, Virus-Like Particle/administration & dosage/*immunology
OTO - NOTNLM
OT  - Dendritic cell
OT  - Influenza
OT  - Innate immunity
OT  - Plant-derived vaccine
OT  - Type 1 response
OT  - Virus-like particle
EDAT- 2018/11/19 06:00
MHDA- 2019/06/04 06:00
CRDT- 2018/11/19 06:00
PHST- 2018/03/19 00:00 [received]
PHST- 2018/10/29 00:00 [revised]
PHST- 2018/10/31 00:00 [accepted]
PHST- 2018/11/19 06:00 [pubmed]
PHST- 2019/06/04 06:00 [medline]
PHST- 2018/11/19 06:00 [entrez]
AID - S0264-410X(18)31496-8 [pii]
AID - 10.1016/j.vaccine.2018.10.099 [doi]
PST - ppublish
SO  - Vaccine. 2018 Dec 18;36(52):8028-8038. doi: 10.1016/j.vaccine.2018.10.099. Epub 
      2018 Nov 14.