1 research outputs found
Design of Fully Synthetic, Self-Adjuvanting Vaccine Incorporating the Tumor-Associated Carbohydrate Tn Antigen and Lipoamino Acid-Based Toll-like Receptor 2 Ligand
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