IMMUNOLOGICAL BASIS FOR PROTECTION IN A MURINE MODEL OF TICK-BORNE ENCEPHALITIS BY A RECOMBINANT ADENOVIRUS CARRYING THE GENE ENCODING THE NS1 NONSTRUCTURAL PROTEIN

The humoral immune response to flaviviruses is mainly directed to the major envelope protein, E, and a glycosylated non-structural protein, NS1. Cell-mediated immune responses, however, appear to be directed ma inly against non-structural proteins, Experiments described here show that a defective recombinant adenovirus (Rad51) containing the gene en coding the NS1 protein of tick-borne encephalitis virus can induce a s trong protective immune response against several pathogenic tick-borne flaviviruses in an experimental animal model, and can enhance the eff icacy of conventional vaccine preparations. A protective immune respon se against a lethal virus challenge can also be induced by the passive transfer of antibodies, B cells or T cells from animals vaccinated wi th Rad51, Raised levels of non-neutralizing antibodies and cytokines a ssociated with a T helper cell-type 1 immune response are also observe d. These data demonstrate the importance of non-structural viral prote ins in the protective immune response against flaviviruses and support the use of non-structural viral proteins as vaccine components.