Pharmacokinetics of human tick-borne encephalitis virus antibody levels after injection with human tick-borne encephalitis immunoglobulin, solvent/detergent treated, FSME-BULIN S/D in healthy volunteers.

This study assessed tick-borne encephalitis virus (TBEV) neutralizing antibody levels after injection of FSME-BULIN S/D (human tick-borne encephalitis immunoglobulin; 0.2 ml/kg body weight) in healthy volunteers. After screening of 18 volunteers for TBEV antibody titers, 12 healthy volunteers with TBEV antibody titers < 5 were entered into the pharmacokinetic part of the study. TBEV antibody titers were analyzed before injection and after 24 h, 48 h, 3 d, 4 d and 8 d. Vital signs, adverse events and laboratory tests for safety were analyzed after intramuscular injection with the immunoglobulin at 4 sites in the gluteal muscles. Injection with 0.2 ml/kg of FSME-BULIN S/D induced a fast increase in, and sustained titers of, neutralizing antibody levels against TBEV. The injections were well tolerated and the safety profile of the product was fully acceptable.

Highly efficient induction of protective immunity by a vaccinia virus vector defective in late gene expression.

Vaccinia viruses defective in the essential gene coding for the enzyme uracil DNA glycosylase (UDG) do not undergo DNA replication and do not express late genes in wild-type cells. A UDG-deficient vaccinia virus vector carrying the tick-borne encephalitis (TBE) virus prM/E gene, termed vD4-prME, was constructed, and its potential as a vaccine vector was evaluated. High-level expression of the prM/E antigens could be demonstrated in infected complementing cells, and moderate levels were found under noncomplementing conditions. The vD4-prME vector was used to vaccinate mice; animals receiving single vaccination doses as low as 10(4) PFU were fully protected against challenge with high doses of virulent TBE virus. Single vaccination doses of 10(3) PFU were sufficient to induce significant neutralizing antibody titers. With the corresponding replicating virus, doses at least 10-fold higher were needed to achieve protection. The data indicate that late gene expression of the vaccine vector is not required for successful vaccination; early vaccinia virus gene expression induces a potent protective immune response. The new vaccinia virus-based defective vectors are therefore promising live vaccines for prophylaxis and cancer immunotherapy.