REPLICATION-DEFECTIVE HIV AS A VACCINE CANDIDATE

Live attenuated vaccines prepared from simian immunodeficiency virus ( SIV) have provided the best protective immunity in challenge experimen ts. In animals vaccinated with attenuated SIV, immune responses may be elicited owing to endogenous expression of native SIV proteins and/or antigen presentation in the native replication site of virus. However , replication-competent viral vaccines raise safety concerns for clini cal trials in humans. To ensure the safety and maintain the immunogeni city of a live, attenuated vaccine, we have developed a replication-de fective HIV pseudotyped with vesicular stomatitis virus G protein (VSV -G), The polymerase gene of HIV was truncated to construct the replica tion-defective HIV. This pseudotyped HIV can infect many cell types, i ncluding human and simian cells, and undergoes only one round of repli cation. Furthermore, antibody immune response can be detected in mice immunized with VSV-G-pseudotyped replication-defective HIV.