Glycan-Modified Virus-like Particles Evoke T Helper Type 1-like Immune Responses
Name
nihms-1682816.pdf
Description
Accepted version
Size
2.34 MB
Format
Adobe PDF
Checksum (MD5)
6bbff3ae44d8b8ca8387216fea076503
Author(s)
Alam, Mohammad Murshid
Jarvis, Cassie M
Hincapie, Robert
McKay, Craig S
Schimer, Jiri
Sanhueza, Carlos A
Xu, Ke
Diehl, Roger C
Finn, MG
Kiessling, Laura L
Date Issued
2021
Journal
ACS Nano
Publisher
American Chemical Society (ACS)
Citation
Alam, Mohammad Murshid, Jarvis, Cassie M, Hincapie, Robert, McKay, Craig S, Schimer, Jiri et al. 2021. "Glycan-Modified Virus-like Particles Evoke T Helper Type 1-like Immune Responses." ACS Nano, 15 (1).
Abstract
© 2021 American Chemical Society. All rights reserved. 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 Qβ 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, Qβ-Man540, elicited DC maturation and induced the expression of the proinflammatory cytokines characteristic of a T helper type 1 (TH1)-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 (Qβ-Ova-Man540) had antigen-specific responses, including the production of CD4+T cells producing the activating cytokines interferon-γand tumor necrosis factor-α. A TH1 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.
MIT Department
Massachusetts Institute of Technology. Department of Chemistry
Terms of Use
Creative Commons Attribution-Noncommercial-Share Alike
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1021/ACSNANO.0C03023
