ABSTRACT
Influenza remains a global public health threat, and the development of new antivirals is crucial to combat emerging drug-resistant influenza strains. In this study, we report the synthesis and evaluation of a sialyl lactosyl (TS)-bovine serum albumin (BSA) conjugate as a potential multivalent inhibitor of the influenza virus. The key trisaccharide component, TS, was efficiently prepared via a chemoenzymatic approach, followed by conjugation to dibenzocyclooctyne-modified BSA via a strain-promoted azide-alkyne cycloaddition reaction. Biophysical and biochemical assays, including surface plasmon resonance, isothermal titration calorimetry, hemagglutination inhibition, and neuraminidase inhibition, demonstrated the strong binding affinity of TS-BSA to the hemagglutinin (HA) and neuraminidase (NA) proteins of the influenza virus as well as intact virion particles. Notably, TS-BSA exhibited potent inhibitory activity against viral entry and release, preventing cytopathic effects in cell culture. This multivalent presentation strategy highlights the potential of glycocluster-based antivirals for combating influenza and other drug-resistant viral strains.
ABSTRACT
Chitotriose (CTS), the hydrolysate of chitosan, is readily soluble in water because of the shorter chain lengths of the oligomers and the free amino groups in the d-glucosamine units. In the current study, we report the synthesis of novel conjugate vaccine Tn-BSA-CTS with chitotriose as built-in adjuvant, along with an evaluation of the effect of adjuvant chitotriose (CTS). Immunological evaluations of the resultant conjugate vaccine revealed that Tn-BSA-CTS could provoke the highest titers of IgG antibodies (102,400). The Tn-BSA-CTS conjugate remarkably enhanced both humoral and cellular immunity. The obtained results demonstrate the potential of CTS as a novel vaccine adjuvant in the development of antitumor vaccine and the covalent linkage of tumor vaccine to CTS might be available strategy to increase the efficacy against cancer.
