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Abstract
The measles virus vaccine (MVbv) is a clinically certified and well-tolerated vaccine strain that has been given both parenterally and mucosally. It has been extensively used in children and has proven to be safe and effective in eliciting protective immunity. This specific strain was therefore chosen to generate a measles viral vector. The genome of the commercial MVbv vaccine strain was isolated, sequenced and a plasmid, p(+)MVb, enabling transcription of the viral antigenome and rescue of MVb, was constructed. Phylogenic and phenotypic analysis revealed that MVbv and the rescued MVb constitute another evolutionary branch within the hitherto classified measles vaccines. Plasmid p(+)MVb was modified by insertion of artificial MV-type transcription units (ATUs) for the generation of recombinant viruses (rMVb) expressing additional proteins. Replication characteristics and immunogenicity of rMVb vectors were similar to the parental MVbv and to other vaccine strains. The expression of the additional proteins was stable over 10 serial virus transfers, which corresponds to an amplification greater than 1020. The excellent safety record and its efficient application as aerosol may add to the usefulness of the derived vectors.
Disclosure of Potential Conflicts of Interest
No potential conflicts of interest were disclosed.
Acknowledgments
MVb vector cloning, rescue and sequencing were performed at the Institute of Molecular Biology, University of Zurich. Further control experiments were performed at Berna Biotech-Crucell, Bern, Switzerland. This study was financially supported by the NIH grant AI-46007 and NIH contract No. N01-AI-60018 to HYN as a PI. We thank Dr Peter Stettler for supplying the MVbv vaccine bulk, Johanna Signer and Jorge Barcos for technical help. We would like to thank Dr Fabian Wild for his generous gift of anti- MV antibodies, and the NIH AIDS Research & Reference Reagent Program for supplying HIV and SIV antibodies.
