GENETIC INFECTION INDUCES PROTECTIVE IN-VIVO IMMUNE-RESPONSES

Drug-induced abortive retroviral infection has been reported to induce both T-cell and B-cell immunity in vivo. We sought to analyze if repl ication-incompetent retroviruses could induce the development of simil arly protective in vivo immune responses in a more desirable fashion. To evaluate retroviral transduction vaccination (genetic infection), a plasmid encoding human CD4 in a retroviral vector was transfected int o the pA317 amphotropic retroviral packaging system. The resulting rep lication defective retrovirus was used to transduce BALB/c mice prior to tumor challenge with human CD4. Immunization elicited specific humo ral and cellular anti-human CD4 responses. We evaluated anti-cell resp onses using a tumor model system. We observed that BALB/c mice challen ged with SP2/0 lymphoma cells develop lethal tumors and die within 7 w eeks of challenge. Cloned SP2/0 cells stably transfected with the huma n cell-surface antigen CD4 also develop tumors in naive mice and succu mb to the tumors in a similar manner to SP2/0 inoculated animals. In c ontrast, CD4 retrovirus-transduced animals, when challenged with the C D4-expressing SP2/0 cells, demonstrated a low incidence of tumors and significantly enhanced survival compared to the mice immunized similar ly with human CD8 retrovirus. These results establish an in vivo tumor challenge system with relevance to the development of protective in v ivo immune responses, and indicate that genetic infection is a useful technique for inducing protective immunity.