TY - JOUR
T1 - Tyrosine-Based Cross-Linking of Peptide Antigens to Generate Nanoclusters with Enhanced Immunogenicity
T2 - Demonstration Using the Conserved M2e Peptide of Influenza A
AU - Wilks, Logan R.
AU - Joshi, Gaurav
AU - Grisham, Megan R.
AU - Gill, Harvinder Singh
N1 - Publisher Copyright:
© 2021 American Chemical Society.
PY - 2021/9/10
Y1 - 2021/9/10
N2 - A method of creating nanoclusters (NCs) from soluble peptide molecules is described utilizing an approach based on a tyrosine-tyrosine cross-linking reaction. A reactive tag comprising histidine and tyrosine residues was introduced at the termini of the peptide molecules. The cross-linking reaction led to the creation of dityrosine bonds within the tag, which allowed for the generation of peptide NCs. We show that it is essential for the reactive tag to be present at both the "N"and "C"termini of the peptide for cluster formation to occur. Additionally, the cross-linking reaction was systematically characterized to show the importance of reaction conditions on final cluster diameter, allowing us to generate NCs of various sizes. To demonstrate the immunogenic potential of the peptide clusters, we chose to study the conserved influenza peptide, M2e, as the antigen. M2e NCs were formulated using the cross-linking reaction. We show the ability of the clusters to generate protective immunity in a dose, size, and frequency dependent manner against a lethal influenza A challenge in BALB/c mice. Taken together, the data presented suggest this new cluster formation technique can generate highly immunogenic peptide NCs in a simple and controllable manner.
AB - A method of creating nanoclusters (NCs) from soluble peptide molecules is described utilizing an approach based on a tyrosine-tyrosine cross-linking reaction. A reactive tag comprising histidine and tyrosine residues was introduced at the termini of the peptide molecules. The cross-linking reaction led to the creation of dityrosine bonds within the tag, which allowed for the generation of peptide NCs. We show that it is essential for the reactive tag to be present at both the "N"and "C"termini of the peptide for cluster formation to occur. Additionally, the cross-linking reaction was systematically characterized to show the importance of reaction conditions on final cluster diameter, allowing us to generate NCs of various sizes. To demonstrate the immunogenic potential of the peptide clusters, we chose to study the conserved influenza peptide, M2e, as the antigen. M2e NCs were formulated using the cross-linking reaction. We show the ability of the clusters to generate protective immunity in a dose, size, and frequency dependent manner against a lethal influenza A challenge in BALB/c mice. Taken together, the data presented suggest this new cluster formation technique can generate highly immunogenic peptide NCs in a simple and controllable manner.
KW - M2e
KW - antigen
KW - influenza
KW - peptide
KW - tyrosine cross-linking
KW - vaccine
UR - http://www.scopus.com/inward/record.url?scp=85114664715&partnerID=8YFLogxK
U2 - 10.1021/acsinfecdis.1c00219
DO - 10.1021/acsinfecdis.1c00219
M3 - Article
C2 - 34432416
AN - SCOPUS:85114664715
SN - 2373-8227
VL - 7
SP - 2723
EP - 2735
JO - ACS Infectious Diseases
JF - ACS Infectious Diseases
IS - 9
ER -