Adjuvant/carrier activity of inactivated tick-borne encephalitis virus

Virus-like or virus-derived particles have been reported to increase the immunogenicity of foreign antigens. In this study formaldehyde-inactivated tick-borne encephalitis virus (TBEV), a potent immunogen in humans, was tested for possible adjuvant/carrier function. The results of our study revealed that substantial antibody titers against very low doses of tetanus toxoid could be obtained when mice were immunized with the antigen covalently coupled to TBEV (using N-succinimidyl-3-(2-pyridyldithio)propionate, a heterobifunctional, cleavable crosslinker containing a disulfide bridge). In contrast, only moderate anti-tetanus toxoid titers were induced by immunizations with a simple mixture of low dose tetanus toxoid and TBEV or when the disulfide bridge of the crosslinker used to couple tetanus toxoid to TBEV was cleaved prior to immunization. The antibody response to TBEV, on the other hand, was not influenced by its linkage to tetanus toxoid. Comparable anti-TBEV titers were obtained following immunization of the animals with either the TBEV-tetanus toxoid conjugate or the mixture of tetanus toxoid and TBEV. Prior application of a TBEV vaccine did not change the antibody response against tetanus toxoid and thus carrier-induced epitopic suppression could be ruled out. The abovementioned adjuvant/carrier properties of TBEV might make it a suitable candidate for use in bi- or multivalent vaccines containing weak immunogens.