APPROACH TO A RETROVIRUS VACCINE - IMMUNIZATION OF MICE AGAINST FRIEND-VIRUS DISEASE WITH A REPLICATION-DEFECTIVE FRIEND MURINE LEUKEMIA-VIRUS

In an initial attempt to test the ability of replication-defective retroviruses to immunize against immunologically related pathogenic viruses, we have worked with the erythroleukemogenic Friend retrovirus complex (FV), which consists of a replication-competent helper component, Friend murine leukemia virus (FMuLV), and a related defective pathogenic component, spleen focus-forming virus (SFFV). An 81-base-pair deletion was introduced into the p15E-encoding region of the env gene of an otherwise replication-competent molecular clone of the FMuLV provirus. After transfection of this clone into cells that package the viral RNA in MuLV coats, infectious virus was released into the culture medium. Mouse fibroblasts infected with this virus, here called DELTAFMuLV, expressed the truncated viral env gene products in their cytoplasm but not on cell surfaces, and culture fluids from these cells did not transmit the infection to fresh mouse fibroblasts. In preliminary experiments, immunization of mice of H-2-congenic BALB/c strains with DELTAFMuLV conferred levels of immunity to FV disease ranging from weak to relatively strong. Immunized mice developed anti-FV IgM and IgG antibodies and cytotoxic T cells. Mice observed for 15 weeks after the first of two immunizations showed no detectable pathology, but DELTAFMuLV DNA was detectable in livers of some immunized mice for at least 3-6 weeks. These results suggest that our approach to development of retrovirus vaccines may be a useful one.