Design of fully synthetic, self-adjuvanting vaccine incorporating the tumor-associated carbohydrate Tn antigen and lipoamino acid-based toll-like receptor 2 ligand

Abdel-Aal, Abu-Baker M., El-Naggar, Dina, Zaman, Mehfuz, Batzloff, Michael and Toth, Istvan (2012) Design of fully synthetic, self-adjuvanting vaccine incorporating the tumor-associated carbohydrate Tn antigen and lipoamino acid-based toll-like receptor 2 ligand. Journal of Medicinal Chemistry, 55 15: 6968-6974. doi:10.1021/jm300822g


Author Abdel-Aal, Abu-Baker M.
El-Naggar, Dina
Zaman, Mehfuz
Batzloff, Michael
Toth, Istvan
Title Design of fully synthetic, self-adjuvanting vaccine incorporating the tumor-associated carbohydrate Tn antigen and lipoamino acid-based toll-like receptor 2 ligand
Journal name Journal of Medicinal Chemistry   Check publisher's open access policy
ISSN 0022-2623
1520-4804
Publication date 2012-08
Sub-type Article (original research)
DOI 10.1021/jm300822g
Volume 55
Issue 15
Start page 6968
End page 6974
Total pages 7
Place of publication Washington, DC, United States
Publisher American Chemical Society
Collection year 2013
Language eng
Abstract Overexpression of certain tumor-associated carbohydrate antigens (TACA) caused by malignant transformation offers promising targets to develop novel antitumor vaccines, provided the ability to break their inherent low immunogenicity and overcome the tolerance of the immune system. We designed, synthesized, and immunologically evaluated a number of fully synthetic new chimeric constructs incorporating a cluster of the most common TACA (known as Tn antigen) covalently attached to T-cell peptide epitopes derived from polio virus and ovalbumin and included a synthetic built-in adjuvant consisting of two 16-carbon lipoamino acids. Vaccine candidates were able to induce significantly strong antibody responses in mice without the need for any additional adjuvant, carrier protein, or special pharmaceutical preparation (e.g., liposomes). Vaccine constructs were assembled either in a linear or in a branched architecture, which demonstrated the intervening effects of the incorporation and arrangement of T-cell epitopes on antibody recognition.
Keyword Relapsed prostate-cancer
Group-A streptococcus
B-cell epitopes
Immunological evaluation
Glycopeptide antigens
Conjugate vaccine
M-protein
Induction
Immunotherapy
Antibodies
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
School of Chemistry and Molecular Biosciences
School of Pharmacy Publications
 
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