Self-assembling peptide for co-delivery of HIV-1 CD8+ T cells epitope and Toll-like receptor 7/8 agonists R848 to induce maturation of monocyte derived dendritic cell and augment polyfunctional cytotoxic T lymphocyte (CTL) response.
Peptide based vaccine that incorporates one or several highly conserved CD8+ T cells epitopes to induce potent cytotoxic T lymphocyte (CTL) response is desirable for some infectious diseases, such as HIV-1 (human immunodeficiency virus-1), and cancers. However, the CD8+ T cells epitope is often weakly immunogenic, and thus requires a specific adjuvant or delivery system to enhance the efficiency. Here we investigated the use of self-assembling peptide EAK16-II based platform to achieve the co-delivery of CD8+ T cells epitope and TLR7/8 agonists (R848 or R837) for augmenting DCs maturation and HIV-1 specific CTL response. HIV-1 CTL epitope SL9 was conjugated with EAK16-II to obtain SL9-EAK16-II, which further spontaneously co-assembled with R848 or R837 in aqueous solution, forming co-assembled nanofibers. Fluorescence spectra and calorimetrical titration revealed the interaction between SL9-EAK16-II assemblies and R848 or R837 via hydrogen bonding and hydrophobic interaction, with the binding affinity (dissociation constant Kd) of 0.62μM or 0.53μM, respectively. Ex vivo generated DCs from HIV-1+ patients pulsed with the SL9-EAK16-II/R848 nanofibers stimulated significantly more polyfunctional SL9 specific CTLs, compared to the DCs pulsed with SL9 alone or the mixture of SL9 and TLR agonist. Furthermore, the nanofibers elicited stronger SL9 specific CTL response in vaccinated mice. Our findings suggest the self-assembling peptide EAK16-II might be used as a new delivery system for peptide based vaccines.
Department of Chemical Engineering, University of Waterloo, 200 University Avenue West, Waterloo, ON N2L 3G1, Canada.
Yong
Y
Ding
Clinical Sciences Division, University of Toronto, Toronto, ON, Canada.
Jun
J
Liu
Department of Chemical Engineering, University of Waterloo, 200 University Avenue West, Waterloo, ON N2L 3G1, Canada.
Sheng
S
Lu
Clinical Sciences Division, University of Toronto, Toronto, ON, Canada.
Justice
J
Igweze
Department of Chemical Engineering, University of Waterloo, 200 University Avenue West, Waterloo, ON N2L 3G1, Canada.
Wen
W
Xu
Clinical Sciences Division, University of Toronto, Toronto, ON, Canada.
Da
D
Kuang
Clinical Sciences Division, University of Toronto, Toronto, ON, Canada.
Chris
C
Zealey
Clinical Sciences Division, University of Toronto, Toronto, ON, Canada.
Daheng
D
Liu
Clinical Sciences Division, University of Toronto, Toronto, ON, Canada.
Alex
A
Gregor
Clinical Sciences Division, University of Toronto, Toronto, ON, Canada.
Ardalan
A
Bozorgzad
Department of Chemical Engineering, University of Waterloo, 200 University Avenue West, Waterloo, ON N2L 3G1, Canada.
Lei
L
Zhang
Clinical Sciences Division, University of Toronto, Toronto, ON, Canada.
Elizabeth
E
Yue
Clinical Sciences Division, University of Toronto, Toronto, ON, Canada.
Shariq
S
Mujib
Clinical Sciences Division, University of Toronto, Toronto, ON, Canada; Department of Immunology, University of Toronto, 1 King's College Circle, Toronto M5S1A8, ON, Canada; Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON M5B1W8, Canada.
Mario
M
Ostrowski
Department of Chemical Engineering, University of Waterloo, 200 University Avenue West, Waterloo, ON N2L 3G1, Canada. Electronic address: p4chen@uwaterloo.ca.
P
P
Chen
D000818:Animals; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D016503:Drug Delivery Systems; D018984:Epitopes, T-Lymphocyte / Q000276:immunology / Q000378:metabolism*; D005260:Female; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D007093:Imidazoles / Q000008:administration & dosage*; D008562:Membrane Glycoproteins / Q000819:agonists* / Q000378:metabolism; D008822:Mice, Transgenic; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D057139:Nanofibers / Q000737:chemistry*; D010316:Particle Size; D011804:Quinolines / Q000008:administration & dosage; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D051199:Toll-Like Receptor 7 / Q000819:agonists* / Q000378:metabolism; D051200:Toll-Like Receptor 8 / Q000819:agonists* / Q000378:metabolism; D014611:Vaccination
C557465:1-(2-methylpropyl)-1H-imidazo(4,5-c)quinolin 4-amine; D018984:Epitopes, T-Lymphocyte; D007093:Imidazoles; D008562:Membrane Glycoproteins; D011804:Quinolines; C552579:TLR8 protein, mouse; C477038:Tlr7 protein, mouse; D051199:Toll-Like Receptor 7; D051200:Toll-Like Receptor 8; C402365:resiquimod
Co-assembly; Co-delivery; Peptide; Vaccine