Open AccessGlycan-Modified Virus-like Particles Evoke T Helper Type 1-like Immune Responses
Author(s) -
Mohammad Murshid Alam,
Cassie M. Jarvis,
Robert Hincapie,
Craig S. McKay,
Jiří Schimer,
Carlos Sanhueza,
Ke Xu,
Roger C. Diehl,
M. G. Finn,
Laura L. Kiessling
Publication year - 2020
Publication title -
acs nano
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.554
H-Index - 382
eISSN - 1936-086X
pISSN - 1936-0851
DOI - 10.1021/acsnano.0c03023
Subject(s) - dc sign , immune system , antigen , proinflammatory cytokine , dendritic cell , microbiology and biotechnology , antigen presentation , endosome , virus like particle , antigen presenting cell , c type lectin , t cell , biology , lectin , glycan , interferon , chemistry , immunology , intracellular , inflammation , glycoprotein , biochemistry , recombinant dna , gene
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-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 (Qβ-Ova-Man 540 ) had antigen-specific responses, including the production of CD4 + T cells producing the activating cytokines interferon-γ and tumor necrosis factor-α. 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.