Hybrid alphavirus–rhabdovirus propagating replicon particles are versatile and potent vaccine vectors
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Edited by Robert A. Lamb, Northwestern University, Evanston, IL, and approved February 20, 2008 (received for review January 11, 2008)
Abstract
Self-propagating, infectious, virus-like particles are generated in animal cell lines transfected with a Semliki Forest virus RNA replicon encoding a single viral structural protein, the vesicular stomatitis virus (VSV) glycoprotein. We show here that these infectious particles, which we call propagating replicons, are potent inducers of neutralizing antibody in animals yet are nonpathogenic. Mice vaccinated with a single dose of the particles generated high titers of VSV-neutralizing antibody and were protected from a subsequent lethal challenge with VSV. Induction of antibody required RNA replication. We also report that additional genes (including an HIV-1 envelope protein gene) expressed from the propagating replicons induced strong cellular immune responses to the corresponding proteins after a single inoculation. Our studies reveal the potential of these particles as simple and safe vaccine vectors inducing strong humoral and cellular immune responses.
Footnotes
- *To whom correspondence should be addressed: E-mail: john.rose{at}yale.edu
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Author contributions: N.F.R., J.P., A.C., and J.K.R. designed research; N.F.R., J.P., and A.C. performed research; N.F.R., J.P., A.C., and J.K.R. analyzed data; and N.F.R., J.P., A.C., and J.K.R. wrote the paper.
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The authors declare no conflict of interest.
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This article is a PNAS Direct Submission.
- © 2008 by The National Academy of Sciences of the USA
