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We assembled a DNA clone containing the 11,161-nt sequence of the prototype rhabdovirus, vesicular stomatitis virus (VSV) MATERIALS AND METHODSPlasmid Construction. The plasmid pVSVFL(+) expressing the 11,161-nt positive-strand (antigenomic) VSV RNA sequence was constructed from four DNA fragments cloned into pBluescript SK(+) (Stratagene). The starting plasmid for the construction, pVSVFL(-), expressed the complete negativesense VSV genomic RNA (Indiana serotype) from a T7 promoter. This plasmid was generated in a nine-step cloning procedure that involved joining the five original cDNA clones of the VSV mRNAs (15-17) with gene junction fragments and terminal fragments. These fragments were generated by reverse transcription and PCR

We developed an AIDS vaccine based on attenuated VSV vectors expressing env and gag genes and tested it in rhesus monkeys. Boosting was accomplished using vectors with glycoproteins from different VSV serotypes. Animals were challenged with a pathogenic AIDS virus (SHIV89.6P). Control monkeys showed a severe loss of CD4+ T cells and high viral loads, and 7/8 progressed to AIDS with an average time of 148 days. All seven vaccinees were initially infected with SHIV89.6P but have remained healthy for up to 14 months after challenge with low or undetectable viral loads. Protection from AIDS was highly significant (p = 0.001). VSV vectors are promising candidates for human AIDS vaccine trials because they propagate to high titers and can be delivered without injection.

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