Virus-like or virus-derived particles have been reported to increase t
he immunogenicity of foreign antigens. In this study formaldehyde-inac
tivated tick-borne encephalitis virus (TBEV), a potent immunogen in hu
mans, was tested for possible adjuvant/carrier function. The results o
f our study revealed that substantial antibody titers against very low
doses of tetanus toxoid could be obtained when mice were immunized wi
th the antigen covalently coupled to TBEV (using N-succinimidyl-3-(2-p
yridyldithio)propionate, a heterobifunctional, cleavable crosslinker c
ontaining 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 c
rosslinker used to couple tetanus toxoid to TBEV was cleaved prior to
immunization. The antibody response to TBEV, on the other hand, was no
t influenced by its linkage to tetanus toxoid. Comparable anti-TBEV ti
ters were obtained following immunization of the animals with either t
he 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 supp
ression could be ruled out. The abovementioned adjuvant/carrier proper
ties of TBEV might make it a suitable candidate for use in bi- or mult
ivalent vaccines containing weak immunogens. (C) 1998 Elsevier Science
Ltd. All rights reserved.