Humoral and cell-mediated immune responses to recombinant vaccinia viruses in mice

Intravenous (i.v.) immunization of mice with recombinant vaccinia viruses stimulated the highest antibody and cytotoxic T lymphocyte (CTL) responses when i.v., intraperitoneal (i.p.), intranasal (i.n.), footpad (f.p.) and tail scarification (t.s.) routes were compared. Intraperitoneal immunization of mice resulted in high CTL activity, but low antibody responses. Antibody levels after i.n., f.p., and t.s. immunization were slightly lower than following i.v. immunization. Although very low levels of CTL primary activity were stimulated by i.n. or f.p. inoculation of recombinant vaccinia virus, levels of secondary CTL activity after in vitro restimulation of splenocytes were as high as those seen from i.v. immunized splenocytes. The effect of the thymidine kinase (TK) phenotype of the virus also was examined. Wildtype (TK positive) viruses replicated to a higher titre in vivo and stimulated higher antibody and CTL responses than a TK negative recombinant virus. A recombinant virus that expressed the TK gene from herpes simplex virus at a low level was intermediate between wildtype and TK negative virus, both in virus replication in vivo and in immunogenicity.