Developing HIV-1 Vaccine through a Synthetic Biology Approach

An effective vaccine for human immunodeficiency virus type-1 (HIV-1) is highly desirable to stem worldwide AIDS pandemic. Although live-attenuated virus vaccine showed excellent efficacy in eliciting host’s immune response, application of such strategy in HIV-1 prevention is hindered by safety concerns due to uncontrolled replication of virus. We recently introduced a new synthetic biology approach to control HIV-1 replication, which entails the manipulation of essential HIV-1 protein biosynthesis through nonsense codon reassignment. This is achieved by the insertion of one or more amber nonsense codons into essential genes of HIV-1. In the presence of an engineered amber suppression machinery, the amber nonsense codon is reassigned into a sense codon to encode an unnatural amino acid. We have successfully demonstrated that we could turn HIV-1 replication on and off in vitro using an unnatural amino acid as the cue. We also engineered HIV-1 genome to contain a genomic copy of the amber suppression machinery, which enables multi-cycle replication control and immunological evaluation in vivo. We envisage that allowing live-attenuated HIV-1 vaccine to replicate only in the presence of unnatural amino acid would improve its safety while still maintains its good efficacy against HIV-1 acquisition. This new synthetic biology approach could be potentially applied to the generation of vaccines against other pathogenic viruses or bacteria.