Induction of protective immunity against pathogenic simian immunodeficiency virus by a foreign receptor-dependent replication of an engineered avirulent virus

In AIDS vaccine strategies, live attenuated vaccines can confer good resist ance against pathogenic virus infections but have the potential risk of ind ucing disease, whereas safer replication-negative strategies such as DNA va ccinations have so far failed to prevent the disease onset. Here, we develo ped a never DNA vaccine strategy to induce restricted replication of an avi rulent virus and evaluated it in a simian immunodeficiency virus (SIV) infe ction model. We generated a chimeric SIV, FMSIV, by replacing SN env with e cotropic Friend murine leukemia virus (FMLV) env to confine its replication to FMLV receptor (mCAT1)-expressing cells. In primate cells lacking mCAT1, FMSIV did not replicate unless mCAT1 was introduced exogenously. Vaccinati on to macaques with both the FMSIV DNA and the mCAT1-expression plasmid DNA induced SIV and resistance against pathogenic SIVmac239 challenge more eff iciently than the Gag-specific cellular Immune responses and resistance aga inst pathogenic SIVmac239 challenge efficiently replication-negative contro l vaccination with the FMSIV DNA alone. This strategy may be useful for dev elopment of safe and effective vaccines against various kinds of pathogenic viruses. (C) 2000 Elsevier Science Ltd. All rights reserved.