PMID- 32790346
OWN - NLM
STAT- MEDLINE
DCOM- 20210514
LR  - 20220127
IS  - 1936-086X (Electronic)
IS  - 1936-0851 (Print)
IS  - 1936-0851 (Linking)
VI  - 15
IP  - 1
DP  - 2021 Jan 26
TI  - Glycan-Modified Virus-like Particles Evoke T Helper Type 1-like Immune Responses.
PG  - 309-321
LID - 10.1021/acsnano.0c03023 [doi]
AB  - Dendritic cells (DCs) are highly effective antigen-presenting cells that shape 
      immune responses. Vaccines that deliver antigen to the DCs can harness their 
      power. DC surface lectins recognize glycans not typically present on host tissue 
      to facilitate antigen uptake and presentation. Vaccines that target these surface 
      lectins should offer improved antigen delivery, but their efficacy will depend on 
      how lectin targeting influences the T cell subtypes that result. We examined how 
      antigen structure influences uptake and signaling from the C-type lectin DC-SIGN 
      (dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin 
      or CD209). Virus-like particles (VLPs) were engineered from bacteriophage Qbeta to 
      present an array of mannoside ligands. The VLPs were taken up by DCs and 
      efficiently trafficked to endosomes. The signaling that ensued depended on the 
      ligand displayed on the VLP: only those particles densely functionalized with an 
      aryl mannoside, Qbeta-Man(540), elicited DC maturation and induced the expression of 
      the proinflammatory cytokines characteristic of a T helper type 1 (T(H)1)-like 
      immune response. This effect was traced to differential binding to DC-SIGN at the 
      acidic pH of the endosome. Mice immunized with a VLP bearing the aryl mannoside, 
      and a peptide antigen (Qbeta-Ova-Man(540)) had antigen-specific responses, including 
      the production of CD4(+) T cells producing the activating cytokines interferon-gamma 
      and tumor necrosis factor-alpha. A T(H)1 response is critical for intracellular 
      pathogens (e.g., viruses) and cancer; thus, our data highlight the value of 
      targeting DC lectins for antigen delivery and validate the utility of DC-targeted 
      VLPs as vaccine vehicles that induce cellular immunity.
FAU - Alam, Mohammad Murshid
AU  - Alam MM
AUID- ORCID: 0000-0002-5646-3309
AD  - Department of Chemistry, Massachusetts Institute of Technology, Cambridge, 
      Massachusetts 02139, United States.
FAU - Jarvis, Cassie M
AU  - Jarvis CM
AUID- ORCID: 0000-0003-4287-4163
AD  - Department of Chemistry, Massachusetts Institute of Technology, Cambridge, 
      Massachusetts 02139, United States.
FAU - Hincapie, Robert
AU  - Hincapie R
AD  - School of Chemistry and Biochemistry, Georgia Institute of Technology, 901 
      Atlantic Drive, Atlanta, Georgia 30332, United States.
FAU - McKay, Craig S
AU  - McKay CS
AD  - School of Chemistry and Biochemistry, Georgia Institute of Technology, 901 
      Atlantic Drive, Atlanta, Georgia 30332, United States.
FAU - Schimer, Jiri
AU  - Schimer J
AD  - School of Chemistry and Biochemistry, Georgia Institute of Technology, 901 
      Atlantic Drive, Atlanta, Georgia 30332, United States.
FAU - Sanhueza, Carlos A
AU  - Sanhueza CA
AD  - School of Chemistry and Biochemistry, Georgia Institute of Technology, 901 
      Atlantic Drive, Atlanta, Georgia 30332, United States.
FAU - Xu, Ke
AU  - Xu K
FAU - Diehl, Roger C
AU  - Diehl RC
AD  - Department of Chemistry, Massachusetts Institute of Technology, Cambridge, 
      Massachusetts 02139, United States.
FAU - Finn, M G
AU  - Finn MG
AUID- ORCID: 0000-0001-8247-3108
AD  - School of Chemistry and Biochemistry, Georgia Institute of Technology, 901 
      Atlantic Drive, Atlanta, Georgia 30332, United States.
FAU - Kiessling, Laura L
AU  - Kiessling LL
AUID- ORCID: 0000-0001-6829-1500
AD  - Department of Chemistry, Massachusetts Institute of Technology, Cambridge, 
      Massachusetts 02139, United States.
LA  - eng
GR  - R01 AI055258/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20200817
PL  - United States
TA  - ACS Nano
JT  - ACS nano
JID - 101313589
RN  - 0 (Antigens)
RN  - 0 (Polysaccharides)
SB  - IM
MH  - Animals
MH  - Antigens
MH  - *Dendritic Cells
MH  - Immunity, Cellular
MH  - Mice
MH  - *Polysaccharides
MH  - T-Lymphocytes
PMC - PMC8249087
MID - NIHMS1682816
OTO - NOTNLM
OT  - DC-SIGN
OT  - TH1-type immunity
OT  - bacteriophage Qbeta
OT  - cytokines
OT  - dendritic cell
OT  - mannose
OT  - virus-like particles
EDAT- 2020/08/14 06:00
MHDA- 2021/05/15 06:00
PMCR- 2022/01/26
CRDT- 2020/08/14 06:00
PHST- 2020/08/14 06:00 [pubmed]
PHST- 2021/05/15 06:00 [medline]
PHST- 2020/08/14 06:00 [entrez]
PHST- 2022/01/26 00:00 [pmc-release]
AID - 10.1021/acsnano.0c03023 [doi]
PST - ppublish
SO  - ACS Nano. 2021 Jan 26;15(1):309-321. doi: 10.1021/acsnano.0c03023. Epub 2020 Aug 
      17.